Podcasts about ca1

Happy New Year from the Mad House!!! Nothin like having a coupla comedians -- Che Durena and Aaron McCann (a Mad House alum) -- to join us for a freshhhh vengeful start to 2025. The ~quartet~ discusses the Ferber baby method, Wife Swap, uncircumcised weenies, and more! Plus, stay tuned for our hotline caller who shares her tip on how to make a quick buck... Call the FUPA Hotline: (347) 480-9006Follow Che:https://www.instagram.com/chedurena/?hl=enFollow Aaron:https://www.instagram.com/mccanncomedy/?hl=enFollow Allie:https://www.instagram.com/defaultprogrammer/?hl=enFollow Maddy:https://www.instagram.com/somaddysmith/?hl=enhttps://www.tiktok.com/@somaddysmith?lang=enAll tour dates: https://maddysmithcomedy.com/Want more Mad House?!Go to https://gasdigitalnetwork.com/ to subscribe!Use promo code MAD to save big on your membership :)Get early access to our weekly episodes on Tuesdays, along with EXCLUSIVE episodes every Thursday.UPCOMING STAND UP DATES:1/2-1/4 SAN DIEGO, CA1/10-1/11 FORT WORTH, TX1/16-1/18 LUTHERVILLE-TIMONIUM, MDProducer: Caroline MazzeiProducer: Ryan DellacagnaSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Maddy and cohost Allie have moved ~house~! They're officially at GaS Digital to record their first episode in the brand new stood!!!! But before they get started, Maddy shares a special message with the people...Call the FUPA Hotline: (347) 480-9006Follow Allie:https://www.instagram.com/defaultprogrammer/?hl=enFollow Maddy:https://www.instagram.com/somaddysmith/?hl=enhttps://www.tiktok.com/@somaddysmith?lang=enAll tour dates: https://maddysmithcomedy.com/Want more Mad House?!Go to https://gasdigitalnetwork.com/ to subscribe!Use promo code MAD to save big on your membership :)Get early access to our weekly episodes on Tuesdays, along with EXCLUSIVE episodes every Thursday.UPCOMING STAND UP DATES:12/27-12/29 ATLANTA, GA1/2-1/4 SAN DIEGO, CA1/10-1/11 FORT WORTH, TX1/16-1/18 LUTHERVILLE-TIMONIUM, MDProducer: Caroline MazzeiProducer: Ryan DellacagnaSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Tina and Hillary cover former Kentucky politician Steve Nunn. Though a son of a former governor, Steve Nunn became a politician in his own right and had a successful career. BUT his life took a dark turn when he murdered his fiancée, shattering his future and reputation. Sources Tina's Story Herald Ledger Estate of woman slain by ex-lawmaker Steve Nunn can garnishee account containing pension payments (https://www.kentucky.com/news/politics-government/article44616372.html) NPR WKU Steve Nunn Apologizes to Ex-Fiance's Family (https://www.wkyufm.org/regional/2013-07-25/steve-nunn-apologizes-to-ex-fiances-family) State Journal ‘God will humble you,' father tells Steve Nunn (https://www.state-journal.com/news/god-will-humble-you-father-tells-steve-nunn/article_e6f97d56-d087-5c31-b8fd-3b7d53316887.html) Wikipedia [Steve Nunn](https://en.wikipedia.org/wiki/Steve_Nunn#:~:text=Stephen%20Roberts%20Nunn%20(born%20November,for%20the%20Commonwealth%20of%20Kentucky.&text=Glasgow%2C%20Kentucky%2C%20U.S.) WPSD Local 6 Kentucky Supreme Court upholds life sentence of former state representative (https://www.wpsdlocal6.com/archive/kentucky-supreme-court-upholds-life-sentence-of-former-state-representative/article_b4f4f79a-2e5f-5760-88dd-e2f44648416d.html) Photos Steve Nunn (https://bloximages.newyork1.vip.townnews.com/wpsdlocal6.com/content/tncms/assets/v3/editorial/3/54/3544fae1-b49c-59fd-9f69-3f73af56bc7f/5d40b6477f7ec.image.jpg?resize=639%2C477)--via WPSD Local 6 Nunn and Ross (https://static01.nyt.com/images/2009/11/13/us/13kentucky_CA3/popup.jpg?quality=75&auto=webp&disable=upscale)--by John Perkins via The New York Times Cemetary where Nunn was arrested (https://static01.nyt.com/images/2009/11/13/us/13kentucky_CA1/popup.jpg?quality=75&auto=webp&disable=upscale)--by Hunter Wilson via The New York Times

@ginandjuice_official @drinksprinter #SummerCocktails #Podcast #CelebrityEndorsements #radioshow #summer Co hosts : Good ol Boy Dave, Good ol Boy Mike, Good ol Boy Sparky, and Good ol Gal Julieanna SUDS  Episode – Are celebrity-endorsed drinks worth the hype? This summer, we're putting them to the test! Join us as we taste and rate canned cocktails from Snoop Dogg and Kylie Jenner. It's a fun, candid, and sometimes surprising episode you won't want to miss. Listen now! We taste and rate the following beer from 1-5: Sprinter Vodka and Juice – Sprinter Spirits, Los Angeles, CA1.           Sprinter Lime 4.5% ABV- SUDS- 22.           Sprinter Peach 4.5% ABV – SUDS-13.           Sprinter Grapefruit – 4.5% ABV- SUDS-24.           Sprinter Black Cherry – 4.5% ABV- SUDS- 1Gin & Juice by Dre and Snoop – By Dre and Snoop, Waverly, NY1.           Citrus – with real juice, Citrus and rose 5.9% ABV – SUDS-22.           Apricot – with real juice, Apricot, honey, bergamot 5.9% ABV –SUDS-33.           Melon – with real juice, watermelon, hibiscus 5.9% ABV SUDS-3 and with Hendricks Gin – SUDS-44.           Passionfruit – with real juice, passionfruit, pineapple, ginger 5.9% ABV- SUDS- 2info@sipssudsandsmokes.com X- @sipssudssmokes IG/FB - @sipssudsandsmokes Sips, Suds, & Smokes® is produced by One Tan Hand Productions using the power of beer, whiskey, and golf.  Available on Apple Podcasts, YouTube Music, Spotify, Pandora, iHeart, and nearly anywhere you can find a podcast.Check out Good ol Boy Dave on 60 Second Reviewshttps://www.instagram.com/goodoleboydave/ Enjoying that cool new Outro Music, it's from Woods & Whitehead – Back Roads Download your copy here:https://amzn.to/2XblorcThe easiest way to find this award winning podcast on your phone is ask Alexa, Siri or Google, “Play Podcast , Sips, Suds, & Smokes” Credits:TITLE: Maxwell SwingPERFORMED BY: Texas GypsiesCOMPOSED BY: Steven R Curry (BMI)PUBLISHED BY: Alliance AudioSparx (BMI)COURTESY OF: AudioSparx TITLE: FlapperjackPERFORMED BY: Texas GypsiesCOMPOSED BY: Steven R Curry (BMI)PUBLISHED BY: Alliance AudioSparx (BMI)COURTESY OF: AudioSparx TITLE: Back RoadsPERFORMED BY: Woods & WhiteheadCOMPOSED BY: Terry WhiteheadPUBLISHED BY: Terry WhiteheadCOURTESY OF: Terry WhiteheadPost production services : Pro Podcast SolutionsAdvertising sales: Contact us directlyContent hosting services:  Earshot, Radio4All, PodBeanProducer: Good ol Gal Julieanna & Good ol Boy DavePrison City Brewing, New England Ipa, Hazy Ipa, Double Ipa, Craft Beer, Beer Tasting, Auburn New York, Beer Review, Citra Hops, Simcoe Hops, Mosaic Hops, Cryo Pop Hop Blend, New York State Brewers Association, Craft Beer Competition, Beer Enthusiasts, Beer Ratings, Hazy Double Ipa, Brewery Takeover, Ipa Beer Styles, Beer PodcastSnoop Dogghttps://en.wikipedia.org/wiki/Snoop_DoggSprinter Vodkahttps://drinksprinter.com/ Gin and Juicehttps://www.ginandjuice.com 

BUFFALO, NY- June 5, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 10, entitled, “Serine racemase expression profile in the prefrontal cortex and hippocampal subregions during aging in male and female rats.” Aging is associated with a decrease in N-methyl-D-aspartate (NMDA) receptor function, which is critical for maintaining synaptic plasticity, learning, and memory. Activation of the NMDA receptor requires binding of the neurotransmitter glutamate and also the presence of co-agonist D-serine at the glycine site. The enzymatic conversion of L-serine to D-serine is facilitated by the enzyme serine racemase (SR). Subsequently, SR plays a pivotal role in regulating NMDA receptor activity, thereby impacting synaptic plasticity and memory processes in the central nervous system. As such, age-related changes in the expression of SR could contribute to decreased NMDA receptor function. However, age-associated changes in SR expression levels in the medial and lateral prefrontal cortex (mPFC, lPFC), and in the dorsal hippocampal subfields, CA1, CA3, and dentate gyrus (DG), have not been thoroughly elucidated. In this new study, researchers Linda Bean, Prodip K. Bose, Asha Rani, and Ashok Kumar from Indiana University School of Medicine, North Florida/South Georgia Veterans Health System, and the University of Florida aimed to determine the SR expression profile, including protein levels and mRNA, for these regions in aged and young male and female Fischer-344 rats. Their results demonstrate a significant reduction in SR expression levels in the mPFC and all hippocampal subfields of aged rats compared to young rats. No sex differences were observed in the expression of SR. “These findings suggest that the decrease in SR levels may play a role in the age-associated reduction of NMDA receptor function in brain regions crucial for cognitive function and synaptic plasticity.” DOI - https://doi.org/10.18632/aging.205841 Corresponding author - Ashok Kumar - kash@ufl.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205841 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, serine racemase, hippocampus, medial prefrontal cortex (mPFC), NMDA receptor About Aging-US Aging publishes research papers in all fields of aging research, including but not limited to aging processes (from yeast to mammals), cellular senescence, age-related diseases (such as cancer and Alzheimer's disease) and their prevention and treatment, anti-aging strategies and drug development, and, importantly, the role of signal transduction pathways in aging (such as mTOR) and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY- February 15, 2024 – A new #research paper was #published on the #cover of Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 3, entitled, “GV1001 reduces neurodegeneration and prolongs lifespan in 3xTg-AD mouse model through anti-aging effects.” GV1001, which mimics the activity of human telomerase reverse transcriptase, protects neural cells from amyloid beta (Aβ) toxicity and other stressors through extra-telomeric function, as noted in our prior in vitro studies. As per a recent phase II clinical trial, it improves cognitive function in patients with moderate to severe dementia. However, the underlying protective mechanisms remain unclear. In this new study, researchers Hyun-Hee Park, Hyuk Sung Kwon, Kyu-Yong Lee, Ye Eun Kim, Jeong-Woo Son, Na-Young Choi, Myung-Hoon Han, Dong Woo Park, Sangjae Kim, and Seong-Ho Koh from Hanyang University Guri Hospital, Hanyang University Graduate School of Biomedical Science and Engineering and Teloid Inc. aimed to investigate the effects of GV1001 on neurodegeneration, senescence, and survival in triple transgenic Alzheimer's disease (AD) (3xTg-AD) mice. “ [...] we hypothesised that GV1001 might have anti-aging effects and improve neurodegeneration and senescence in vivo as a possible mechanism for its beneficial effects on AD.” GV1001 (1 mg/kg) was subcutaneously injected into old 3xTg-AD mice thrice a week until the endpoint for sacrifice, and survival was analysed. Magnetic resonance imaging (MRI) and Prussian blue staining (PBS) were performed to evaluate entry of GV1001 entrance into the brain. Diverse molecular studies were performed to investigate the effect of GV1001 on neurodegeneration and cellular senescence in AD model mice, with a particular focus on BACE, amyloid beta1-42 (Aβ1-42), phosphorylated tau, volume of dentate gyrus, β-galactosidase positive cells, telomere length, telomerase activity, and ageing-associated proteins. GV1001 crossed the blood-brain barrier, as confirmed by assessing the status of ferrocenecarboxylic acid-conjugated GV1001 using magnetic resonance imaging and PBS. GV1001 increased the survival of 3xTg-AD mice. It decreased BACE and Aβ1-42 levels, neurodegeneration (i.e., reduced CA1, CA3 and dentate gyrus volume, decreased levels of senescence-associated β-galactosidase positive cells, and increased telomere length and telomerase activity), and levels of ageing-associated proteins. “We suggest that GV1001 exerts anti-ageing effects in 3xTg-AD mice by reducing neurodegeneration and senescence, which contributes to improved survival.” DOI - https://doi.org/10.18632/aging.205489 Corresponding authors - Sangjae Kim - chiron@gemvax.com, and Seong-Ho Koh - ksh213@hanyang.ac.kr Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

MedLink Neurology Podcast is delighted to feature selected episodes from BrainWaves, courtesy of James E Siegler MD, its originator and host. BrainWaves is an academic audio podcast whose mission is to educate medical providers through clinical cases and topical reviews in neurology, medicine, and the humanities, and episodes originally aired from 2016 to 2021.  Originally released: December 27, 2018 As I'm sitting in a coffee shop in upstate New York this holiday season, procrastinating on the various papers that need writing, bills that need paying, and Christmas cards that need writing, I can't help but feel comforted by the warm relief of a cup of coffee. The rich aroma and jolting heat, which come with the promise of productivity. There's nothing like it. So before resigning to my post-holiday to-do list, I thought I would start the day off re-mastering a prior show we put out in 2017 on the neuroscience behind your morning mocha. Enjoy! Produced by James E Siegler. Music by Andy Cohen and Little Glass Men. Sound effects by Mike Koenig and Daniel Simion. BrainWaves' podcasts and online content are intended for medical education only and should not be used for clinical decision-making. Be sure to follow us on Twitter @BrainWavesaudio for the latest updates to the podcast. REFERENCES Ferré S. An update on the mechanisms of the psychostimulant effects of caffeine. J Neurochem 2008;105(4):1067-79. PMID 18088379Martín ED, Buño W. Caffeine-mediated presynaptic long-term potentiation in hippocampal CA1 pyramidal neurons. J Neurophysiol 2003;89(6):3029-38. PMID 12783948Nawrot P, Jordan S, Eastwood J, Rotstein J, Hugenholtz A, Feeley M. Effects of caffeine on human health. Food Addit Contam 2003;20(1):1-30. PMID 12519715Park CA, Kang CK, Son YD, et al. The effects of caffeine ingestion on cortical areas: functional imaging study. Magn Reson Imaging 2014;32(4):366-71. PMID 24512799Pelchovitz DJ, Goldberger JJ. Caffeine and cardiac arrhythmias: a review of the evidence. Am J Med 2011;124(4):284-9. PMID 21435415Ribeiro JA, Sebastião AM. Caffeine and adenosine. J Alzheimers Dis 2010;20 Suppl 1:S3-15. PMID 20164566  We believe that the principles expressed or implied in the podcast remain valid, but certain details may be superseded by evolving knowledge since the episode's original release date.

Live from Center Stage at ASA's annual meeting, Dr. Adam Striker hosts a panel of anesthesiologists at different career stages. He joins Dr. Abigail Schirmer, a CA1, along with late career anesthesiologist, Dr. Mark Singleton, and recent retiree, Dr. Richard Himes, in conversation about how the specialty has evolved, what they wish other generations understood better, their expectations for the future, and more. Recorded October 2023.

The final episode from Rocklands! Ethan Pringle joins me for a fireside chat on my last day in South Africa. We share a wrap-up of the trip, and tackle Patron questions about Ethan's back injury and rehab, his favorite climbing areas in California, why I still do “No Hangs”, my send of Octopussy, projecting tips, how I use the Tindeq, Ethan's most epic bat hangs, mental health struggles and setbacks, challenging your perceived limits, why Ethan thinks I should spend more time training on commercial gym sets, my thoughts about Rocklands overall, and much more!Check out Rocky Talkie!RockyTalkie.com/NuggetUse this link to get 10% off your first order of backcountry radios!Check out Crimpd!crimpd.comOr download the Crimpd app!Check out AG1!drinkAG1.com/NUGGETUse this link to get a free year's supply of vitamin D + 5 travel packs!Check out Wonderful Pistachios!WonderfulPistachios.com to learn more!Check out Green Chef!greenchef.com/60nuggetUse code "60NUGGET" at checkout for 60% off plus free shipping!We are supported by these amazing BIG GIVERS:Leo Franchi, Michael Roy, David Lahaie, Robert Freehill, Jeremiah Johnson, Scott Donahue, Eli Conlee, Skyler Maxwell, Craig Lee, Mark and Julie Calhoun, Yinan Liu, Renzollama, Zach Emery, and Brandt MickolasBecome a Patron:patreon.com/thenuggetclimbingShow Notes:  thenuggetclimbing.com/episodes/qa-7Nuggets:0:03:51 – Rocklands Recap:0:03:51 – My recap of being sick, and how fast time flies on a trip0:11:55 – Comparing my trips to Magic Wood and Rocklands, and my main takeaway0:13:07 – Ethan's trip recap, and remaining goals0:18:22 – Recap of my journey on Black Shadow0:22:32 – Some of the other hard boulders I tried0:24:06 – The line between having a “bad” vs “good” trip0:25:29 – Expectations vs. reality, and resetting your reference points to find gratitude0:28:02 – Patron Questions:0:28:02 – Shawn's Question: Ethan's back injury/rehab, his plans to lift weights, and the rigors of bouldering in Rocklands0:34:04 – Shawn's Question: No Hangs, finding your max load for training, and my current approach to finger strength0:38:40 – Rajiv's Question: Top routes that have inspired Ethan, Connor Herson's repeat of Black Beard's Tears, and Ethan's FA in Greenland0:41:47 – Rajiv's Question: China Beach in Rumney0:43:05 – Rajiv's Question: Chris Linder's route Window of Opportunity0:47:59 – Travis' Question: My send of Octopussy, the process, and projecting tips0:56:40 – Colin's Question: Where Ethan developed his love for climbing, being a gym rat at heart, and his early climbing in CA1:00:10 – Colin's Question: Go-to climbing areas near San Francisco, Ethan's thoughts on Jailhouse, and areas in northern CA1:03:42 – Colin's Question: Bouldering exploration in the Eastern Sierras, and unfinished business at Shuteye Ridge1:09:58 – Colin's Question: Ethan's thoughts on the bouldering near LA1:13:11 – Cody's Question: Tindeq protocols, edge sizes, and some notes about my finger training on the trip1:19:40 – Patreon plug, and info about Q&As1:21:26 – Daniel's Question: Ethan's thoughts on bat hangs1:28:02 – Alan's Question: Which climber's superpowers we wish we had1:31:44 – Jacob's Question: Ethan's thoughts on mental health struggles, and how that plays into his climbing1:35:28 – Why loving yourself won't make you lose your edge1:39:02 – Wren's Question: My thoughts on sport climbing in the future, and meeting climbing partners on the road1:44:20 – Jacob's Question: Favorite sport climbing destinations in the US1:46:25 – Unpacking the word “favorite”1:47:15 – Lars' Question: Dealing with setbacks and mental struggles1:49:33 – The beauty of Rocklands1:51:07 – Connor's Question: Most memorable boulders, and life list boulders1:57:03 – Cooper's Question: Favorite home crags near the Bay that Ethan never gets tired of, and remaining highballs in Bishop1:59:13 – Luke's Question: Challenging your perceived limits2:09:08 – More Thoughts About Rocklands:2:09:08 – Why Ethan thinks I should spend more time on commercial gym sets2:10:40 – My thoughts on the climbing in Rocklands, and why I was hesitant to talk about it2:19:28 – Sweet spot grades in different areas, and wanting to be good enough to enjoy weird or unpleasant climbs2:22:59 – We need that 18-year-old Moonboard energy2:24:32 – Wanting to come back, and wrap up

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551580v1?rss=1 Authors: Mahapatra, S., Takahashi, T. Abstract: After exocytosis, release sites are cleared of vesicular residues to be replenished with transmitter-filled vesicles. Endocytic and scaffold proteins are thought to underlie this mechanism. However, physiological significance of the site-clearance mechanism among diverse central synapses remains unknown. Here, we tested this using action-potential evoked EPSCs in mouse brainstem and hippocampal slices in physiologically optimized condition. Pharmacological block of endocytosis enhanced synaptic depression at brainstem calyceal fast synapses, whereas it attenuated synaptic facilitation at hippocampal CA1 slow synapses. Block of scaffold protein activity likewise enhanced synaptic depression at calyceal synapses but had no effect at hippocampal synapses. At calyceal synapses, enhancement of synaptic depression by blocking endocytosis or scaffold activity occurred at nearly identical time courses with a time constant of several milliseconds starting immediately after the stimulation onset. Neither endocytic nor scaffold inhibitors prolonged the recovery from short-term depression. We conclude that endocytic release-site clearance can be a universal phenomenon supporting vesicle replenishment across fast and slow synapses, whereas presynaptic scaffold mechanism likely plays a specialized role in vesicle replenishment predominantly at fast synapses. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.549180v1?rss=1 Authors: Jain, A., Nakahata, Y., Watabe, T., Rusina, P., South, K. E., Adachi, K., Yan, L., Simorowski, N., Furukawa, H., Yasuda, R. Abstract: Behavioral time scale plasticity (BTSP), is a form of non-Hebbian plasticity induced by integrating pre- and postsynaptic components separated by behavioral time scale (seconds). BTSP in the hippocampal CA1 neurons underlies place cell formation. However, the molecular mechanisms underlying this behavioral time scale (eligibility trace) and synapse specificity are unknown. CaMKII can be activated in a synapse-specific manner and remain active for a few seconds, making it a compelling candidate for the eligibility trace during BTSP. Here, we show that BTSP can be induced in a single dendritic spine using 2-photon glutamate uncaging paired with postsynaptic current injection temporally separated by behavioral time scale. Using an improved CaMKII sensor, we saw no detectable CaMKII activation during this BTSP induction. Instead, we observed a dendritic, delayed, and stochastic CaMKII activation (DDSC) associated with Ca2+ influx and plateau 20-40 s after BTSP induction. DDSC requires both pre-and postsynaptic activity, suggesting that CaMKII can integrate these two signals. Also, optogenetically blocking CaMKII 30 s after the BTSP protocol inhibited synaptic potentiation, indicating that DDSC is an essential mechanism of BTSP. IP3-dependent intracellular Ca2+ release facilitates both DDSC and BTSP. Thus, our study suggests that the non-synapse specific CaMKII activation provides an instructive signal with an extensive time window over tens of seconds during BTSP. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.25.550518v1?rss=1 Authors: Voroslakos, M., Zhang, Y., McClain, K., Huszar, R., Rothstein, A., Buzsaki, G. Abstract: Brain states fluctuate between exploratory and consummatory phases of behavior. These state changes affect both internal computation and the organism's responses to sensory inputs. Understanding neuronal mechanisms supporting exploratory and consummatory states and their switching requires experimental control of behavioral shifts and collecting sufficient amounts of brain data. To achieve this goal, we developed the ThermoMaze, which exploits the animal's natural warmth-seeking homeostatic behavior. By decreasing the floor temperature and selectively heating unmarked areas, mice avoid the aversive state by exploring the maze and finding the warm spot. In its design, the ThermoMaze is analogous to the widely used water maze but without the inconvenience of a wet environment and, therefore, allows the collection of physiological data in many trials. We combined the ThermoMaze with electrophysiology recording, and report that spiking activity of hippocampal CA1 neurons during sharp-wave ripple events encode the position of the animal. Thus, place-specific firing is not confined to locomotion and associated theta oscillations but persist during waking immobility and sleep at the same location. The ThermoMaze will allow for detailed studies of brain correlates of immobility, preparatory-consummatory transitions and open new options for studying behavior-mediated temperature homeostasis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.27.550869v1?rss=1 Authors: Heuer, S. E., Nickerson, E. W., Howell, G. R., Bloss, E. B. Abstract: The disconnection of neuronal circuits through synaptic loss is presumed to be a major driver of age-related cognitive decline. Age-related cognitive decline is heterogeneous, yet whether genetic mechanisms differentiate successful from unsuccessful cognitive decline through synaptic structural mechanisms remains unknown. Previous work using rodent and primate models leveraged various techniques to suggest that age-related synaptic loss is widespread on pyramidal cells in prefrontal cortex (PFC) circuits but absent on those in area CA1 of the hippocampus. Here, we examined the effect of aging on synapses on projection neurons forming a hippocampal-cortico-thalamic circuit important for spatial working memory tasks from two genetically distinct mouse strains that exhibit susceptibility (C57BL/6J) or resistance (PWK/PhJ) to cognitive decline during aging. Across both strains, synapses on the CA1-to-PFC projection neurons appeared completely intact with age. In contrast, we found synapse loss on PFC-to-nucleus reuniens (RE) projection neurons from aged C57BL/6J but not PWK/PhJ mice. Moreover, synapses from aged PWK/PhJ mice but not from C57BL/6J exhibited morphological changes that suggest increased synaptic efficiency to depolarize the parent dendrite. Our findings suggest resistance to age-related cognitive decline results in part by age-related synaptic adaptations, and identification of these mechanisms in PWK/PhJ mice could uncover new therapeutic targets for promoting successful cognitive aging and extending human health span. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.19.549533v1?rss=1 Authors: Haast, R. A., Kashyap, S., Ivanov, D., Yousif, M. D., DeKraker, J., Poser, B. A., Khan, A. R. Abstract: We present a comprehensive study on the non-invasive measurement of hippocampal perfusion. Using high-resolution 7 Tesla arterial spin labelling data, we generated robust perfusion maps and observed significant variations in perfusion among hippocampal subfields, with CA1 exhibiting the lowest perfusion levels. Notably, these perfusion differences were robust and detectable even within five minutes and just fifty perfusion-weighted images per subject. To understand the underlying factors, we examined the influence of image quality metrics, various tissue microstructure and morphometry properties, macrovasculature and cytoarchitecture. We observed higher perfusion in regions located closer to arteries, demonstrating the influence of vascular proximity on hippocampal perfusion. Moreover, ex vivo cytoarchitectonic features based on neuronal density differences appeared to correlate stronger with hippocampal perfusion than morphometric measures like gray matter thickness. These findings emphasize the interplay between microvasculature, macrovasculature, and metabolic demand in shaping hippocampal perfusion. Our study expands the current understanding of hippocampal physiology and its relevance to neurological disorders. By providing in vivo evidence of perfusion differences between hippocampal subfields, our findings have implications for diagnosis and potential therapeutic interventions. In conclusion, our study provides a valuable resource for extensively characterising hippocampal perfusion. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.19.549725v1?rss=1 Authors: Parkins, E. V., Brager, D. H., Rymer, J. K., Burwinkel, J. M., Rojas, D., Tiwari, D., Hu, Y.-C., Gross, C. Abstract: MicroRNAs are an emerging class of synaptic regulators. These small noncoding RNAs post-transcriptionally regulate gene expression, thereby altering neuronal pathways and shaping cell-to-cell communication. Their ability to rapidly alter gene expression and target multiple pathways makes them interesting candidates in the study of synaptic plasticity. Here, we demonstrate that the proconvulsive microRNA miR-324-5p regulates excitatory synapse structure and function in the hippocampus of mice. Both Mir324 knockout (KO) and miR-324-5p antagomir treatment significantly reduce dendritic spine density in the hippocampal CA1 subregion, and Mir324 KO, but not miR-324-5p antagomir treatment, shift dendritic spine morphology, reducing the proportion of thin, 'unstable' spines. Western blot and quantitative Real-Time PCR revealed changes in protein and mRNA levels for potassium channels, cytoskeletal components, and synaptic markers, including MAP2 and Kv4.2, which are essential for long-term potentiation (LTP). In line with these findings, slice electrophysiology revealed that LTP is severely impaired in Mir324 KO mice, while baseline excitatory activity remains unchanged. Overall, this study demonstrates that miR-324-5p regulates dendritic spine density, morphology, and plasticity in the hippocampus, potentially via multiple cytoskeletal and synaptic modulators. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.13.548837v1?rss=1 Authors: Moldwin, T., Azran, L. S., Segev, I. Abstract: The brain modifies synaptic strengths to store new information via long-term potentiation (LTP) and long-term depression (LTD). Evidence has mounted that long-term plasticity is controlled via concentrations of calcium ([Ca2+]) in postsynaptic spines. Several mathematical models describe this phenomenon, including those of Shouval, Bear, and Cooper (SBC) (Shouval et al., 2002, 2010) and Graupner and Brunel (GB)(Graupner & Brunel, 2012). Here we suggest a generalized version of the SBC and GB models, based on a fixed point -- learning rate (FPLR) framework, where the synaptic [Ca2+] specifies a fixed point toward which the synaptic weight approaches asymptotically at a [Ca2+]-dependent rate. The FPLR framework offers a straightforward phenomenological interpretation of calcium-based plasticity: the calcium concentration tells the synaptic weight where it is going and how fast it goes there. The FPLR framework can flexibly incorporate various experimental findings, including the existence of multiple regions of [Ca2+] where no plasticity occurs, or plasticity in cerebellar Purkinje cells, where the directionality of calcium-based synaptic changes is thought to be reversed relative to cortical and hippocampal neurons. We also suggest a modeling approach that captures the dependency of late-phase plasticity stabilization on protein synthesis. We demonstrate that due to the asymptotic, saturating nature of synaptic changes in the FPLR rule, the result of frequency- and spike-timing-dependent plasticity protocols are weight-dependent. Finally, we show how the FPLR framework can explain plateau potential-induced place field formation in hippocampal CA1 neurons, also known as behavioral time scale plasticity (BTSP). Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.11.548438v1?rss=1 Authors: Peerboom, C. N. E., Wijne, T. B., Wierenga, C. J. Abstract: During the first two postnatal weeks intraneuronal chloride concentrations in rodents gradually decrease, causing a shift from depolarizing to hyperpolarizing {gamma}-aminobutyric acid (GABA) responses. GABAergic depolarization in the immature brain is crucial for the formation and maturation of excitatory synapses, but when GABAergic signaling becomes inhibitory it no longer promotes synapse formation. Here we examined the role of chloride transporters in developing postnatal hippocampal neurons using furosemide, an inhibitor of the chloride importer NKCC1 and chloride exporter KCC2 with reported anticonvulsant effects. We treated organotypic hippocampal cultures made from 6 to 7-day old mice with 200 M furosemide from DIV1 to DIV8. Using perforated patch clamp recordings we observed that the GABA reversal potential was depolarized after acute furosemide application, but after a week of furosemide treatment the GABA reversal potential but was more hyperpolarized compared to control. Expression levels of the chloride cotransporters were unaffected after one week furosemide treatment. This suggests that furosemide inhibited KCC2 acutely, while prolonged treatment resulted in (additional) inhibition of NKCC1, but we cannot exclude changes in HCO3-. We assessed the effects of accelerating the GABA shift by furosemide treatment on inhibitory synapses onto CA1 pyramidal cells. Directly after cessation of furosemide treatment at DIV9, inhibitory synapses were not affected. However at DIV21, two weeks after ending the treatment, we found that the frequency of inhibitory currents was increased, and VGAT puncta density in stratum Radiatum was increased. In addition, cell capacitance of CA1 pyramidal neurons was reduced in furosemide-treated slices at DIV21 in an activity-dependent manner. Our results suggest that furosemide indirectly promotes inhibitory transmission, but the underlying mechanism remains unresolved. The furosemide-induced increase in inhibitory transmission might constitute an additional mechanism via which furosemide reduces seizure susceptibility in the epileptic brain. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.10.547981v1?rss=1 Authors: Arndt, K. C., Gilbert, E. T., Klaver, L. M. F., Kim, J., Buhler, C. M., Basso, J. C., McKenzie, S. A., English, D. F. Abstract: Neuronal oscillations support information transfer by temporally aligning the activity of anatomically distributed 'writer' and 'reader' cell assemblies. High-frequency oscillations (HFOs) such as hippocampal CA1 sharp-wave ripples (SWRs; 100-250 Hz) are sufficiently fast to initiate synaptic plasticity between assemblies and are required for memory consolidation. HFOs are observed in parietal and midline cortices including granular retrosplenial cortex (gRSC). In offline brain states (e.g. quiet wakefulness) gRSC HFOs co-occur with CA1 SWRs, while in online states (e.g. ambulation) HFOs persist with the emergence of theta oscillations. The mechanisms of gRSC HFO oscillations, specifically whether the gRSC can intrinsically generate HFOs, and which layers support HFOs across states, remain unclear. We addressed these issues in behaving mice using optogenetic excitation in individual layers of the gRSC and high density silicon-probe recordings across gRSC layers and hippocampus CA1. Optogenetically induced HFOs (iHFOs) could be elicited by depolarizing excitatory neurons with 100 ms half-sine wave pulses in layer 2/3 (L2/3) or layer 5 (L5) though L5 iHFOs were of lower power than in L2/3. Critically, spontaneous HFOs were only observed in L2/3 and never in L5. Intra-laminar monosynaptic connectivity between excitatory and inhibitory neurons was similar across layers, suggesting other factors restrict HFOs to L2/3. To compare HFOs in online versus offline states we analyzed, separately, HFOs that did or did not co-occur with CA1 SWRs. Using current-source density analysis we found uniform synaptic inputs to L2/3 during all gRSC HFOs, suggesting layer-specific inputs may dictate the localization of HFOs to L2/3. HFOs occurring without SWRs were aligned with the descending phase of both gRSC and CA1 theta oscillations and were coherent with CA1 high frequency gamma oscillations (50-80 Hz). These results demonstrate that gRSC can internally generate HFOs without rhythmic inputs and that HFOs occur exclusively in L2/3, coupled to distinct hippocampal oscillations in online versus offline states. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.10.548420v1?rss=1 Authors: Machado, J. P., Almeida, V., Zuardi, A. W., Hallak, J. E., Crippa, J. A., Schwambach Vieira, A. Abstract: Background: Cannabidiol (CBD), one of the main cannabinoids present in the female flowers of Cannabis sativa, has been a therapeutic alternative for a plurality of disorders. Previous investigation has already provided insights into the CBD molecular mechanism, however, there is no transcriptome data for CBD effects on hippocampal subfields. Here, we explore the transcriptomic changes in dorsal and ventral CA1 of adult mice hippocampus after 100 mg/kg of CBD administration (i.p.) for one or seven consecutive days. Methods: C57BL/6JUnib mice were divided into 4 groups treated with either vehicle or CBD for 1 or 7 days. The collected brains were sectioned and the hippocampal subregions were laser microdissected for RNA-Seq analysis. Data alignment, quantification and analysis were conducted with the STAR Aligner/DESeq2/clusterProfiler R-package pipeline. Results: We found changes in gene expression in CA1 neurons after single and multiple CBD administrations. Furthermore, the enrichment analysis of differentially expressed genes following 7 days of CBD administration indicates a widespread decrease in the expression levels of electron transport chain and ribosome biogenesis transcripts, while chromatin modifications and synapse organization transcripts were increased. Conclusion: This dataset provides a significant contribution toward advancing our comprehension of the mechanisms responsible for CBD effects on hippocampal neurons. The findings suggest that CBD prompts a significant reduction in energy metabolism genes and the protein translation machinery in CA1 neurons. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.28.546918v1?rss=1 Authors: Zheng, L., Gao, Z., Doner, S., Oyao, A., Forloines, M., Grilli, M., Barnes, C. A., Ekstrom, A. D. Abstract: Older adults show declines in spatial memory, although the extent of these alterations is not uniform across the healthy older population. Here, we investigate the stability of neural representations for the same and different spatial environments in a sample of younger and older adults using high-resolution functional magnetic resonance imaging (fMRI) of the medial temporal lobe. Older adults showed, on average, less distinct neural patterns between spatial environments and more variable neural patterns within a single environment. We also found a positive association between spatial distance discrimination and the distinctiveness of neural patterns between environments. Our analyses suggested that one source for this association was the extent of informational connectivity to CA1 from other subfields, which was dependent on age, while another source was the fidelity of signals within CA1 itself, which was independent of age. Together, our findings suggest both age-dependent and independent neural contributions to spatial memory performance. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.21.546025v1?rss=1 Authors: Sauvage, M. M., Ku, S.-P., Atucha, E., Alavi, N., Yoshida, M., Csicsvari, J. Abstract: How the coordination of neuronal spiking activity and brain rhythms between hippocampal subregions supports memory function remains elusive. We studied interregional coordination of CA3 neuronal spiking activity with CA1 theta oscillations by recording electrophysiological signals along the proximodistal axis of the hippocampus in rats performing a high memory demand recognition memory task adapted from humans. We found that CA3 population spiking activity occurs preferentially at the peak of distal CA1 theta oscillations only when animals recalled previously encountered stimuli. In addition, decoding analyses revealed that only population cell firing of proximal CA3 together with that of distal CA1 can predict memory performance in the present non-spatial task. Overall, our work demonstrates an important role of the synchronization of CA3 neuronal activity with CA1 theta oscillations for successful recognition memory. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.03.539260v1?rss=1 Authors: Irwin, A. B., Martina, V., Sint Jago, S. C., Bahabry, R., Schreiber, A. M., Lubin, F. D. Abstract: Dysregulation of long non-coding RNAs (lncRNAs) have been associated with Alzheimer's disease (AD). However, the functional role of lncRNAs in AD remains unclear. Here, we report a crucial role for the lncRNA Neat1 in astrocyte dysfunction and memory deficits associated with AD. Transcriptomics analysis show abnormally high expression levels of NEAT1 in the brains of AD patients relative to aged-matched healthy controls, with the most significantly elevated levels in glial cells. In a human transgenic APP-J20 (J20) mouse model of AD, RNA-fluorescent in situ hybridization characterization of Neat1 expression in hippocampal astrocyte versus non-astrocyte cell populations revealed a significant increase in Neat1 expression in astrocytes of male, but not female, mice. This corresponded with increased seizure susceptibility in J20 male mice. Interestingly, Neat1 deficiency in the dCA1 in J20 male mice did not alter seizure threshold. Mechanistically, Neat1 deficiency in the dorsal area CA1 of the hippocampus (dCA1) J20 male mice significantly improved hippocampus-dependent memory. Neat1 deficiency also remarkably reduced astrocyte reactivity markers suggesting that Neat1 overexpression is associated with astrocyte dysfunction induced by hAPP/A{beta} in the J20 mice. Together, these findings indicate that abnormal Neat1 overexpression may contribute to memory deficits in the J20 AD model not through altered neuronal activity, but through astrocyte dysfunction. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.27.538511v1?rss=1 Authors: Chamberland, S., Grant, G., Machold, R. P., Nebet, E. R., Tian, G., Hanani, M., Kullander, K., Tsien, R. W. Abstract: Hippocampal somatostatin-expressing (Sst) GABAergic interneurons (INs) exhibit considerable anatomical and functional heterogeneity. Recent single cell transcriptome analyses have provided a comprehensive Sst-IN subtype census, a plausible molecular ground truth of neuronal identity whose links to specific functionality remain incomplete. Here, we designed an approach to identify and access subpopulations of Sst-INs based on transcriptomic features. Four mouse models based on single or combinatorial Cre- and Flp- expression differentiated functionally distinct subpopulations of CA1 hippocampal Sst-INs that largely tiled the morpho-functional parameter space of the Sst-INs superfamily. Notably, the Sst;;Tac1 intersection revealed a population of bistratified INs that preferentially synapsed onto fast-spiking interneurons (FS-INs) and were both necessary and sufficient to interrupt their firing. In contrast, the Ndnf;;Nkx2-1 intersection identified a population of oriens lacunosum-moleculare (OLM) INs that predominantly targeted CA1 pyramidal neurons, avoiding FS-INs. Overall, our results provide a framework to translate neuronal transcriptomic identity into discrete functional subtypes that capture the diverse specializations of hippocampal Sst-INs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.25.538286v1?rss=1 Authors: Taxidis, J., Madruga, B., Melin, M. D., Lin, M., Golshani, P. Abstract: Hippocampal spiking sequences encode and link behavioral information across time. How inhibition sculpts these sequences remains unknown. We performed longitudinal voltage imaging of CA1 parvalbumin- and somatostatin- expressing interneurons in mice during an odor-cued working memory task, before and after training. During this task, pyramidal odor-specific sequences encode the cue throughout a delay period. In contrast, most interneurons encoded odor delivery, but not odor identity, nor delay time. Population inhibition was stable across days, with constant field turnover, though some cells retained odor-responses for days. At odor onset, a brief, synchronous burst of parvalbumin cells was followed by widespread membrane hyperpolarization and then rebound theta-paced spiking, synchronized across cells. Two-photon calcium imaging revealed that most pyramidal cells were suppressed throughout the odor. Positive pyramidal odor-responses coincided with interneuronal rebound spiking; otherwise, they had weak odor-selectivity. Therefore, inhibition increases the signal-to-noise ratio of cue representations, which is crucial for entraining downstream targets. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.24.537999v1?rss=1 Authors: Lisgaras, C. P., Scharfman, H. E. Abstract: Interictal spikes (IIS) are a common type of abnormal electrical activity in animal models of Alzheimers disease (AD) and AD patients. The brain regions where IIS are largest are not known but are important because such data would suggest sites that contribute to IIS generation. Because hippocampus and cortex exhibit altered excitability in AD models, we asked where IIS are largest along the cortical-CA1-dentate gyrus (DG) dorso-ventral axis. Because medial septal (MS) cholinergic neurons are overactive when IIS typically occur, we also tested the novel hypothesis that silencing the medial septohippocampal cholinergic neurons selectively would reduce IIS. We used 3 models of AD, Tg2576 mice, presenilin 2 knockout mice, and the Ts65Dn mouse model of Downs syndrome. To selectively silence MS cholinergic neurons, Tg2576 mice were bred with ChAT-Cre mice and offspring mice were injected in the MS with AAV encoding inhibitory designer receptors exclusively activated by designer drugs. We recorded EEG along the cortical-CA1-DG axis using silicon probes during wakefulness, slow-wave sleep (SWS) and rapid eye movement (REM) sleep. We detected IIS in all transgenic mice but not age-matched controls. IIS were detectable throughout the cortical-CA1-DG axis and were primarily during REM sleep. In all 3 models, IIS amplitudes were significantly greater in the DG granule cell layer vs. CA1 pyramidal layer or overlying cortex. Selective chemogenetic silencing of MS cholinergic neurons significantly reduced IIS frequency during REM sleep without affecting the overall duration or number of REM sleep bouts. Maximal IIS amplitude in the DG of 3 AD mouse models suggests that the DG could be one of the areas that contribute to IIS generation. Selectively reducing MS cholinergic tone could be a new strategy to reduce IIS in AD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.21.537874v1?rss=1 Authors: Ontiveros-Angel, P., Vega-Torres, J. D., Simon, T. B., Williams, V., Inostroza-Nives, Y., Alvarado-Crespo, N., Vega Gonzalez, Y., Pompolius, M., Katzka, W., Lou, J., Sharafeddin, F., De La Pena, I., Dong, T., Gupta, A., Viet, C. T., Febo, M., Obenaus, A., Figueroa, J. D. Abstract: Background: Childhood overweight/obesity is associated with the development of stress-related psychopathology. However, the pathways connecting childhood obesity to stress susceptibility remain poorly understood. Here, we used a systems biology approach to determine linkages underlying obesity-induced stress susceptibility. Methods: Sixty-two (62) adolescent Lewis rats (PND21) were fed for four weeks with a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a matched control diet (CD, 13% kcal from fat). Subsequently, a group of rats (n = 32) was exposed to a well-established 31-day model of predator exposures and social instability (PSS). The effects of the WD and PSS were assessed with a comprehensive battery of behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), high throughput 16S ribosomal RNA gene sequencing for gut microbiome profiling, hippocampal microglia morphological and gene analysis, and gene methylation status of the stress marker, FKBP5. Parallel experiments were performed on human microglial cells (HMC3) to examine molecular mechanisms by which palmitic acid primes these cells to aberrant responses to cortisol. Results: Rats exposed to the WD and PSS exhibited deficits in sociability indices and increased fear and anxiety-like behaviors, food consumption, and body weight. WD and PSS interacted to alter indices of microstructural integrity within the hippocampal formation (subiculum) and subfields (CA1). Microbiome diversity and taxa distribution revealed that WD/PSS exposure caused significant shifts in the diversity of gut dominant bacteria and decreased the abundance of various members of the Firmicutes phylum, including Lachnospiracae NK4A136. Interestingly, the WD and PSS synergized to promote hippocampal microglia morphological and gene signatures implicated in neuroinflammation. These alterations were associated with changes in the microbiome, and in the expression and methylation status of the corticosterone receptor chaperone rat gene Fkbp5. HMC3 responses to cortisol were markedly disrupted after incubating cells in palmitate, shown by morphological changes and pro-inflammatory cytokine expression and release. Notably, these effects were partly mediated by the human FKBP5 gene. Conclusions: The combination of psychosocial stress and poor diet during adolescence has a deleterious synergistic impact on brain health. This study enhances our understanding of mechanisms and adaptations by which obesogenic environments shape the maturational trajectories of common neurobiological correlates of resilience. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A rare sight at Brunton Park for a while - goals galore, as United and Stockport play out a humdinger of a game in CA1 but is a point not a huge amount of use to either side in their push for automatic promotion?In this episode of The Brunton Bugle, the lads look back on a 2-2 draw that was a brilliant advert for League Two football - lots of chat about Simmo's tactical switch, Jon Mellish scoring with his appendage and some of the best away fans we've seen at BP this season. We also look ahead to the Cumbrian Classic/A595 Derby/just another game (delete as appropriate) as United make the trip down the coast to take on Barrow - we catch-up with Freya from BBC Radio Cumbria's excellent "Out of the Blue" CUFC and Barrow podcast about how the Bluebirds are getting on this season - with discussion about the change from following a non-league side to an EFL side, how Pete Wild's first season in-charge at Holker St has got on and the growing "rivalry" between the two sets of fans..There's also a news update and a round-up of how Ex-Blues got in in the last week.Your host Lee Rooney is in Liverpool and is joined via the wonders of the internet by Dan MacLennan in Carlisle. You can find us on Twitter @bruntonbugle, Facebook (search for "Brunton Bugle") and email us with any questions, suggestions and feedback to bruntonbugle@gmail.com.-------------------We're pleased to confirm that Carlisle United Supporters' Club London Branch will be sponsoring the podcast once again this season! As part of this sponsorship, they will be providing some useful info for us to share ahead of each away trip in terms of pubs, public transport changes, places to eat etc.The London Branch is open to all Carlisle United fans across the world - whether you're based in the capital, New York, Timbuktu, Berlin or even Cumbria itself! To find out more, visit their website at www.carlislelondonbranch.org Hosted on Acast. See acast.com/privacy for more information.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.18.536607v1?rss=1 Authors: Geva-Sagiv, M., Dimsdale-Zucker, H. R., Williams, A. B., Ranganath, C. Abstract: Recollection of real-world events is often accompanied by a sense of being in the place where the event transpired. Convergent evidence suggests the hippocampus plays a key role in supporting episodic memory by associating information with the time and place it was originally encountered. This representation is reinstated during memory retrieval. However, little is known about the roles of different subfields of the human hippocampus in this process. Research in humans and non-human animal models have suggested that spatial environmental boundaries have a powerful influence on spatial and episodic memory, as well as hippocampal representations of contexts and events. Here, we used high-resolution fMRI to investigate how boundaries influence hippocampal activity patterns during the recollection of objects encountered in different spatial contexts. During the encoding phase, participants viewed objects once in a naturalistic virtual reality task, in which they passively explored two rooms in one of two houses. Following the encoding phase, participants were scanned while they recollected items in the absence of any spatial contextual information. Our behavioral results demonstrated that spatial context memory was enhanced for objects encountered near a boundary. Activity patterns in CA1 carried information about the spatial context associated with each of these boundary items. Exploratory analyses revealed that memory for the room in which each object was studied was correlated with the fidelity of retrieved spatial context representations in anterior parahippocampal cortex and subiculum. Our results highlight the privileged role of boundaries in CA1 and suggest more generally a close relationship between memory for spatial contexts and representations in the hippocampus and parahippocampal region. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.18.537149v1?rss=1 Authors: Saghafi, S., Rumbell, T. H., Gurev, V., Kozloski, J. C., Tamagnini, F., Wedgwood, K. C., Diekman, C. O. Abstract: Alzheimer's disease (AD) is believed to occur when abnormal amounts of the proteins amyloid beta and tau aggregate in the brain, resulting in a progressive loss of neuronal function. Hippocampal neurons in transgenic mice with amyloidopathy or tauopathy exhibit altered intrinsic excitability properties. We introduce a novel parameter inference technique, deep hybrid modeling (DeepHM), that combines deep learning with biophysical modeling to map experimental data recorded from hippocampal CA1 neurons in transgenic AD mice and age-matched wildtype littermate controls to the parameter space of a conductance-based CA1 model. Although mechanistic modeling and machine learning methods are by themselves powerful tools for approximating biological systems and making accurate predictions from data, when used in isolation these approaches suffer from distinct shortcomings: model and parameter uncertainty limit mechanistic modeling, whereas machine learning methods disregard the underlying biophysical mechanisms. DeepHM addresses these shortcomings by using conditional generative adversarial networks (cGANs) to provide an inverse mapping of data to mechanistic models that identifies the distributions of mechanistic modeling parameters coherent to the data. Here, we demonstrate that DeepHM accurately infers parameter distributions of the conductance-based model and outperforms a Markov chain Monte Carlo method on several test cases using synthetic data. We then use DeepHM to estimate parameter distributions corresponding to the experimental data and infer which ion channels are altered in the Alzheimer's mouse models compared to their wildtype controls at 12 and 24 months. We find that the conductances most disrupted by tauopathy, amyloidopathy, and aging are delayed rectifier potassium, transient sodium, and hyperpolarization-activated potassium, respectively. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.18.537377v1?rss=1 Authors: Xiao, K., Li, Y., Chitwood, R. A., Magee, J. C. Abstract: Behavioral timescale synaptic plasticity (BTSP) is a type of non-Hebbian synaptic plasticity reported to underlie place field formation in the hippocampal CA1 neurons. Despite this important function, the molecular mechanisms underlying BTSP are poorly understood. The Calcium-calmodulin-dependent protein kinase II (CaMKII) is activated by synaptic transmission-mediated calcium influx and its subsequent phosphorylation is central to synaptic plasticity. Because the activity of CaMKII is known to outlast the event triggering phosphorylation, we hypothesized it could be involved in the extended timescale of the BTSP process. To examine the role of CaMKII in BTSP, we performed whole-cell in-vivo and in-vitro recordings in CA1 pyramidal neurons from mice engineered to have a point mutation at the autophosphorylation site (T286A) causing accelerated signaling kinetics. Here we demonstrate a profound deficit in synaptic plasticity, strongly suggesting that CaMKII signaling is required for BTSP. This study elucidates part of the molecular mechanism of BTSP and provides insight into the function of CaMKII in place cell formation and ultimately learning and memory. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.15.536995v1?rss=1 Authors: Tarusawa, E., Hasegawa, S., Noda, D., Kawamura, N., Fukazawa, Y., Watanabe, M., Hirabayashi, T., Yagi, T. Abstract: Clustered protocadherins (cPcdhs) are candidates for the neural circuit formation; however, the localization of cPcdhs in pre- and post-synaptic compartments has not been well characterized. Here we examined the localization of cPcdh{gamma} proteins in the mouse hippocampal CA1 region using light and electron microscopy. From postnatal day 7 to 21, cPcdh{gamma} immunosignals were detected in approximately 40-60% of spines of pyramidal cells. SDS-digested freeze-fracture replica labelling revealed that cPcdh{gamma} immunolabeling was found in 50% of PSD 95-positive postsynaptic profiles but only in less than 10% of vGluT1-positive pre-synaptic terminals. Interestingly, cPcdh{gamma}-positive pre-synaptic terminal was exclusively accompanied by cPcdh{gamma}-positive postsynaptic counterpart. In addition, electrophysiological investigations revealed that the miniature excitatory postsynaptic current frequency in cPcdh{gamma} cKO mice was significantly higher than that in wild-type mice. These results suggest that cPcdh{gamma} proteins are unequally distributed in the pre- and post-synaptic membrane during neural circuit development and regulate the number of excitatory synapses. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.07.536066v1?rss=1 Authors: Vinci-Booher, S., Schlichting, M., Preston, A., Pestilli, F. Abstract: The hippocampus is a complex brain structure composed of subfields that each have distinct cellular organizations. While the volume of hippocampal subfields displays age-related changes that have been associated with inference and memory functions, the degree to which the cellular organization within each subfield is related to these functions throughout development is not well understood. We employed an explicit model testing approach to characterize the development of tissue microstructure and its relationship to performance on two inference tasks, one that required memory (memory-based inference) and one that could be completed based on perceptually available information (perception-based inference). We found that each subfield had a unique developmental trajectory in terms of its cellular organization. While the SUB displayed a linear trajectory, DG, CA1, and CA2/3 subfields displayed non-linear trajectories that interacted with sex in CA2/3. We found that the DG was related to memory-based inference performance and that the SUB, a subfield outside of the hippocampus proper, was related to perception-based inference; neither relationship interacted with age. Results suggest that cellular organization within hippocampal subfields undergo distinct developmental trajectories that may underlie changes in inference and memory performance throughout development. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.03.535350v1?rss=1 Authors: Marasco, A., Tribuzi, C., Iuorio, A., Migliore, M. Abstract: Efficient and accurate large-scale networks are a fundamental tool in modelling brain areas, to advance our understanding of neuronal dynamics. However, their implementation faces two key issues: computational efficiency and heterogeneity. Computational efficiency is achieved using simplified neurons, whereas there are no practical solutions available to solve the problem of reproducing in a large-scale network the experimentally observed heterogeneity of the intrinsic properties of neurons. This is important, because the use of identical nodes in a network can generate artifacts which can hinder an adequate representation of the properties of a real network. To this aim, we introduce a mathematical procedure to generate an arbitrary large number of copies of simplified hippocampal CA1 pyramidal neurons and interneurons models, which exhibit the full range of firing dynamics observed in these cells - including adapting, nonadapting and bursting. For this purpose, we rely on a recently published adaptive generalized leaky integrate-and-fire (A-GLIF) modeling approach, leveraging on its ability to reproduce the rich set of electrophysiological behaviours of these types of neurons under a variety of different stimulation currents. The generation procedure is based on a perturbation of model's parameters related to the initial data, firing block, and internal dynamics, and suitably validated against experimental data to ensure that the firing dynamics of any given cell copy remains within the experimental range. This allows to obtain heterogeneous copies with mathematically controlled firing properties. A full set of heterogeneous neurons composing the CA1 region of a rat hippocampus (approximately 500K neurons), are provided in a database freely available in the live paper section of the EBRAINS platform. By adapting the underlying A-GLIF framework, it will be possible to extend the numerical approach presented here to create, in a mathematically controlled manner, an arbitrarily large number of non-identical copies of cell populations with firing properties related to other brain areas. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.28.534599v1?rss=1 Authors: Levi, A., Aviv, N., Stark, E. Abstract: Learning from examples and adapting to new rules are fundamental attributes of human cognition. However, it is unclear what conditions allow for fast and successful learning. To determine how rapidly freely-moving mice can learn a new rule, we designed a fully automated two-alternative forced choice visual discrimination paradigm in which the rules governing the task can change between sessions. We find that animals can learn a new rule during the very first block of trials. The propensity for single session learning improves over time and can be accurately predicted based on animal experience and rule difficulty. When conditions for generalization from a previous rule are more favorable, mice perform single session learning with higher success rates. Units recorded from hippocampal region CA1 during a previously-learned visual rule exhibit task-related place fields and state-dependent modulation. A mouse trained on visual rules can learn an intra-cortical rule, generated by direct activation of hippocampal CA1 pyramidal cells. Thus, after establishing procedural learning of a paradigm, mice continue to perform and improve at associative operant learning of new rules. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.26.534277v1?rss=1 Authors: Wilson, L. R., Plummer, N. W., Evsyukova, I. Y., Patino, D., Stewart, C. L., Smith, K. G., Fry, S. A., Deal, A. L., Kilonzo, V. W., Sciolino, N. R., Cushman, J. D., jensen, p. Abstract: Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, the precise temporal dynamics of their release in the hippocampus during behavior is unknown. In addition, new animal models are required to probe the effects of altered catecholamine synthesis on release dynamics and contextual learning. Utilizing GRABNE and GRABDA sensors, in vivo fiber photometry, and two new mouse models of altered locus coeruleus norepinephrine (LC-NE) synthesis, we investigate norepinephrine (NE) and dopamine (DA) release dynamics in dorsal hippocampal CA1 during contextual fear conditioning. We report that aversive foot-shock increases both NE and DA release in dorsal CA1, while freezing behavior associated with recall of fear memory is accompanied by decreased release. Partial loss of LC-NE synthesis reveals that NE release dynamics are modulated by sex. Moreover, we find that recall of recent fear memory is sensitive to both partial and complete loss of LC-NE synthesis throughout prenatal and postnatal development, similar to prior observations of mice with global loss of NE synthesis beginning postnatally. In contrast, remote recall is compromised only by complete loss of LC-NE synthesis beginning prenatally. Overall, these findings provide novel insights into the role of NE in contextual fear and the precise temporal dynamics of both NE and DA during freezing behavior, and highlight a complex relationship between genotype, sex, and NE signaling. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.27.534420v1?rss=1 Authors: Ratigan, H. C., Krishnan, S., Smith, S., Sheffield, M. E. J. Abstract: Memory retrieval of fearful experiences is essential for survival, but can be maladaptive if not appropriately suppressed. Fear memories can be acquired through contextual fear conditioning (CFC) which relies on the hippocampus. The thalamic subregion Nucleus Reuniens (NR) is necessary for contextual fear extinction and strongly projects to hippocampal subregion CA1. However, the NR-CA1 pathway has not been investigated during behavior, leaving unknown its role in contextual fear memory retrieval. We implement a novel head-restrained virtual reality CFC paradigm, and show that inactivation of the NR-CA1 pathway prolongs fearful freezing epochs, induces fear generalization, and delays extinction. We use in vivo sub-cellular imaging to specifically record NR-axons innervating CA1 before and after CFC. We find NR-axons become selectively tuned to freezing only after CFC, and this activity is well-predicted by an encoding model. We conclude that the NR-CA1 pathway actively suppresses fear responses by disrupting ongoing hippocampal-dependent contextual fear memory retrieval. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.25.534233v1?rss=1 Authors: Virga, D. M., Hamilton, S., Osei, B., Morgan, A., Zamponi, E., Park, N. J., Hewitt, V. L., Zhang, D., Gonzalez, K. C., Bloss, E., Polleux, F., Lewis, T. L. Abstract: Neuronal mitochondria play important roles beyond ATP generation, including Ca2+ uptake, and therefore have instructive roles in synaptic function and neuronal response properties. Mitochondrial morphology differs significantly in the axon and dendrites of a given neuronal subtype, but in CA1 pyramidal neurons (PNs) of the hippocampus, mitochondria within the dendritic arbor also display a remarkable degree of subcellular, layer-specific compartmentalization. In the dendrites of these neurons, mitochondria morphology ranges from highly fused and elongated in the apical tuft, to more fragmented in the apical oblique and basal dendritic compartments, and thus occupy a smaller fraction of dendritic volume than in the apical tuft. However, the molecular mechanisms underlying this striking degree of subcellular compartmentalization of mitochondria morphology are unknown, precluding the assessment of its impact on neuronal function. Here, we demonstrate that this compartment-specific morphology of dendritic mitochondria requires activity-dependent, Camkk2-dependent activation of AMPK and its ability to phosphorylate two direct effectors: the pro-fission Drp1 receptor Mff and the recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers a new activity-dependent molecular mechanism underlying the extreme subcellular compartmentalization of mitochondrial morphology in dendrites of neurons in vivo through spatially precise regulation of mitochondria fission/fusion balance. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.17.533028v1?rss=1 Authors: Jeong, H., K Namboodiri, V. M., Jung, M. W., Andermann, M. L. Abstract: Cortical neurons activated during recent experiences often reactivate with dorsal hippocampal CA1 sharp-wave ripples (SWRs) during subsequent rest. Less is known about cortical interactions with intermediate hippocampal CA1, whose connectivity, functions, and SWRs differ from those of dorsal CA1. We identified three clusters of visual cortical excitatory neurons that are excited together with either dorsal or intermediate CA1 SWRs, or suppressed before both SWRs. Neurons in each cluster were distributed across primary and higher visual cortices and co-active even in the absence of SWRs. These ensembles exhibited similar visual responses but different coupling to thalamus and pupil-indexed arousal. We observed a consistent activity sequence: (i) suppression of SWR-suppressed cortical neurons, (ii) thalamic silence, and (iii) activation of the cortical ensemble preceding and predicting intermediate CA1 SWRs. We propose that the coordinated dynamics of these ensembles relay visual experiences to distinct hippocampal subregions for incorporation into different cognitive maps. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.15.532748v1?rss=1 Authors: Fernandez-Moncada, I., B. Fundazuri, U., Lavanco, G., Bollmohr, N., Hachaguer, P., Dalla Tor, T., Mountadem, S., Serrat, R., Bellocchio, L., Cannich, A., Nasu, Y., Campbell, R. E., Drago, F., Bouzier-Sore, A.-K., Pellerin, L., Bolanos, J. P., Bonvento, G., Barros, L. F., Oliet, S. H. R., Panatier, A., Marsicano, G. Abstract: Control of brain energy metabolism and regulation of synaptic activity through gliotransmission are two important ways, through which astrocytes contribute to mental functions. However, the potential functional and molecular links between these two astrocyte-dependent processes have been scantly explored so far. Here we show that a lactate-dependent shift of glycolysis underlies the production of the gliotransmitter D-serine by acute activation of astrocyte type-1 cannabinoid (CB1) receptors, thereby gating synaptic and cognitive processes. Acute cannabinoid application causes a CB1 receptor-dependent rapid and reversible increase of lactate production and release in primary astrocyte cultures. As shown before, mutant mice lacking the CB1 receptor gene in astrocytes (GFAP-CB1-KO) were impaired in a novel object recognition (NOR) task. Notably, this phenotype was rescued not only by the gliotransmitter D-serine, but also by its precursor L-serine. Surprisingly, the administration of lactate also reverted the memory impairment of GFAP-CB1-KO mice. This rescue effect was abolished by in vivo blockade of the astrocyte-specific phosphorylated pathway (PP), which diverts glycolysis towards L-serine synthesis, suggesting that lactate itself might promote the accumulation of this amino acid. Consistent with this idea, lactate increased the co-agonist occupancy of CA1 post-synaptic hippocampal NMDA receptors in a PP-dependent manner. By establishing a mechanistic link between lactate, serine availability, synaptic activity and behavior, these results reveal an unforeseen functional connection between energy metabolism and gliotransmission to control cognitive processes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.15.532740v1?rss=1 Authors: Roessler, N., Jungenitz, T., Sigler, A., Bird, A., Mittag, M., Rhee, J., Deller, T., Cuntz, H. J., Brose, N., Schwarzacher, S., Jedlicka, P. Abstract: Dendritic spines are crucial for excitatory synaptic transmission as the size of a spine head correlates with the strength of its synapse. The distribution of spine head sizes follows a lognormal-like distribution with more small spines than large ones. We analysed the impact of synaptic activity and plasticity on the spine size distribution in adult-born hippocampal granule cells from rats with induced homo- and heterosynaptic long-term plasticity in vivo and CA1 pyramidal cells from Munc-13-1-Munc13-2 knockout mice with completely blocked synaptic transmission. Neither induction of extrinsic synaptic plasticity nor the blockage of presynaptic activity degrades the lognormal-like distribution but changes its mean, variance and skewness. The skewed distribution develops early in the life of the neuron. Our findings and their computational modelling support the idea that intrinsic synaptic plasticity is sufficient for the generation, while a combination of intrinsic and extrinsic synaptic plasticity maintains lognormal like distribution of spines. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this VETgirl veterinary podcast, we interview Dr. Joerg Steiner, med.vet., Dr.med.vet., PhD, DACVIM, DECVIM-CA, AGAF, Regents Professor at Texas A&M University. He will review the most recent updates in acute canine pancreatitis (ACP) and an exciting new therapeutic option, PANOQUELL®-CA1 (fuzapladib sodium for injection). Acute canine pancreatitis is far more common than previously believed but until now, the treatment has been purely symptomatic. Dr. Steiner will be talking about the disease, diagnosis, prognosis, and updates in treatment. Tune in to learn about pancreatitis and its new, innovative solution.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.03.531039v1?rss=1 Authors: Valk, S. L., Engert, V., Puhlmann, L., Linz, R., Caldairou, B., Bernasconi, A., Bernasconi, N., Bernhardt, B. C., Singer, T. Abstract: The hippocampus forms a central modulator of the HPA-axis, impacting the regulation of stress on brain structure, function, and behavior. The current study assessed whether three different types of 3-months mental training modules geared towards nurturing a) attention-based mind-fulness, b) socio-affective skills, or c) socio-cognitive abilities may impact hippocampal integrity by reducing stress. We evaluated mental training-induced changes in hippocampal subfield vol-ume and intrinsic functional connectivity, based on resting-state fMRI connectivity analysis in a group of healthy adults (N=332). We then related these changes to changes in diurnal and chronic cortisol levels. We observed increases in bilateral cornu ammonis volume (CA1-3) fol-lowing the 3-months compassion-based module targeting socio-affective skills (Affect module), as compared to socio-cognitive skills (Perspective module) or a waitlist cohort that did not un-dergo an intervention. Structural changes were paralleled by increases in functional connectivity of CA1-3 when fostering socio-affective as compared to socio-cognitive skills. Moreover, train-ing-related changes in CA1-3 structure and function consistently correlated with reduction in cortisol output. In sum, we provide a link between socio-emotional behavioral intervention, CA1-3 structure and function, and cortisol reductions in healthy adults. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.24.529922v1?rss=1 Authors: Michon, F.-X., Laplante, I., Bosson, A., Robitaille, R., Lacaille, J.-C. Abstract: Plasticity of principal cells and inhibitory interneurons underlies hippocampal memory. Bidirectional modulation of somatostatin cell mTORC1 activity, a crucial translational control mechanism in synaptic plasticity, causes parallel changes in hippocampal CA1 somatostatin interneuron (SOM-IN) long-term potentiation and hippocampus-dependent memory, indicating a key role in learning. However, SOM-IN activity changes and behavioral correlates during learning, and the role of mTORC1 in these processes, remain ill-defined. To address these questions, we used two-photon Ca2+ imaging from SOM-INs during a virtual reality goal-directed spatial memory task in head-fixed control mice (SOM-IRES-Cre mice) or in mice with conditional knockout of Rptor (SOM-Rptor-KO mice) to block mTORC1 activity in SOM-INs. We found that control mice learn the task, but SOM-Raptor-KO mice exhibit a deficit. Also, SOM-IN Ca2+ activity became increasingly related to reward localization during learning in control mice but not in SOM-Rptor-KO mice. Four types of SOM-IN activity patterns related to reward location were observed, "reward off sustained", "reward off transient", "reward on sustained" and "reward on transient", and these responses showed global remapping after reward relocation in control but not SOM-Rptor-KO mice. Thus, SOM-INs develop mTORC1-dependent spatial coding related to learning reward localization. This coding may bi-directionally interact with pyramidal cells and other structures to represent and consolidate reward location. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.21.529420v1?rss=1 Authors: Wick, Z. C., Philipsberg, P. A., Lamsifer, S. I., Kohler, C., Katanov, E., Feng, Y., Humphrey, C., Shuman, T. Abstract: The precise timing of neuronal spiking relative to the brain's endogenous oscillations (i.e., phase-locking or spike-phase coupling) has long been hypothesized to coordinate cognitive processes and maintain excitatory-inhibitory homeostasis. Indeed, disruptions in theta phase-locking have been described in models of neurological diseases with associated cognitive deficits and seizures, such as Alzheimer's disease, temporal lobe epilepsy, and autism spectrum disorders. However, due to technical limitations, determining if phase-locking causally contributes to these disease phenotypes has not been possible until recently. To fill this gap and allow for the flexible manipulation of single-unit phase-locking to on-going endogenous oscillations, we developed PhaSER, an open-source tool that allows for phase-specific manipulations. PhaSER can deliver optogenetic stimulation at defined phases of theta in order to shift the preferred firing phase of neurons relative to theta in real-time. Here, we describe and validate this tool in a subpopulation of inhibitory neurons that express somatostatin (SOM) in the CA1 and dentate gyrus (DG) regions of the dorsal hippocampus. We show that PhaSER is able to accurately deliver a photo-manipulation that activates opsin+ SOM neurons at specified phases of theta in real-time in awake, behaving mice. Further, we show that this manipulation is sufficient to alter the preferred firing phase of opsin+ SOM neurons without altering the referenced theta power or phase. All software and hardware requirements to implement real-time phase manipulations during behavior are available online (https://github.com/ShumanLab/PhaSER). Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.20.529330v1?rss=1 Authors: Levy, S. J., Hasselmo, M. E. Abstract: The hippocampus plays a central role in episodic memory and spatial navigation. Hippocampal neurons form unique representational codes in different spatial environments, which may provide a neural substrate for context that can trigger memory recall or enable performance of context-guided memory tasks. However, new learning often occurs in a familiar location, requiring that location's representation to be updated without erasing the previously existing memory representations that may be adaptive again in the future. To study how new learning affects a previously acquired spatial memory representation, we trained mice to perform two plus maze tasks across nine days in the sequence Turn Right 1 - Go East - Turn Right 2 (three days each), while we used single-photon calcium imaging to record the activity of hundreds of neurons in dorsal CA1. One cohort of mice performed the entire experiment on the same maze (One-Maze), while the second cohort performed the Go East task on a unique maze (Two-Maze). We hypothesized that CA1 representations in One-Maze mice would exhibit more change in the spatial patterns of neuronal activity on the maze from Turn Right 1 to Turn Right 2 than would be seen in Two-Maze mice. Indeed, changes in single unit activity and in the population code were larger in the One-Maze group. We further show evidence that Two-Maze mice utilize a separate neural representation for each maze environment. Finally, we found that remapping across the two Turn Right epochs did not involve an erasure of the representation for the first Turn Right experience, as many neurons in mice from both groups maintained Turn Right-associated patterns of activity even after performing the Go East rule. These results demonstrate that hippocampal activity patterns remap in response to new learning, that remapping is greater when experiences occur in the same spatial context, and that throughout remapping information from each experience is preserved. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

We have the always-inspiring Julian Molina on the podcast today. Despite losing his leg at a young age, Julian has pushed himself to become the amazing BMX rider and human he is today. Hit play and learn something new about the man himself. 0:00 - Intro Julian and Jeff Z / New Podcast sponsor?2:45 - Recent big bowl crash / Crashing8:35 - How Julian lost his leg18:05 - Julian's first bike25:05 - Getting a prostatic41:30 - Defining moment / red bull Event / X Games Real BMX50:15 - Learning tailwhips1:03:00 - Family life / BMX life1:12:15 - Getting on GT BMX1:13:30 - First trip to the U.S / Learning English1:24:45- Stew Johnson, Master Two1:33:10 - Buying a farm1:41:30 - GT BMX CYFT Premiere / Hanging out in CA1:46:00 - Future Plans1:57:00 - Wrap up / Make sure to follow Julian's Jewelry account @julians_jewelry7 on IGGuest:Julian Molina: https://www.instagram.com/julianmolina_bmx/Jeff Zielinski: https://www.instagram.com/jeffzphoto/Hosts:Ryan Fudger: https://www.instagram.com/fyanrudger/Dennis Enarson: https://www.instagram.com/dennisenarson/Vans BMX: https://www.vans.com/en-us

Lutein and zeaxanthin isomers benefits during high screen exposure University of Georgia, July 10, 2022 An exciting new peer reviewed publication based on ongoing research on macular carotenoids from the University of Georgia demonstrates that supplementation with lutein and zeaxanthin isomers can protect against a growing issue among the general population -- the undesirable effects of prolonged exposure to high-energy blue light emitted from digital screens of computers, tablets and smartphones. Lutein and zeaxanthin isomers -- known as the macular carotenoids -- are natural filters of high-energy blue light. High-energy blue light reaches deep into the eye and can harm the macula -- the region of the eye responsible for highest visual acuity- by promoting the production of free radicals. Short-term effects can cause eye fatigue while long-term exposure can lead to a progressive loss of visual function. This is the first study to examine the impact of macular carotenoids supplementation to protect visual health and performance, improve sleep quality and reduce eye strain and fatigue during prolonged exposure to blue light emitting digital screens. The study was a 6-month randomized, double-blind, placebo-controlled supplementation trial with 48 healthy, young adults with screen time exposure of at least 6 hours daily. Subjects were evaluated at baseline, 3-months and 6-months for MPOD (Macular Pigment Optical Density) and markers of visual performance including contrast sensitivity, photostress recovery and disability glare. Sleep quality, which is affected by blue light exposure, and physical indicators of excessive screen use were also measured. The results show that supplementing with lutein and zeaxanthin significantly improved macular pigment optical density, visual performance and indicators of excessive screen use, including eye strain and fatigue and headache frequency. Sleep quality also improved significantly.   Study explores the effects of eating dark chocolate on the brain Isfahan University of Medical Science (Iran), July 14, 2022   Elham Kalantarzedeh, Maryam Radahmadi and Parham Reisi, three researchers at Isfahan University of Medical Science in Iran have recently carried out a study on rats investigating the impact of different dark chocolate dietary patterns on synapses in a specific region of the brain, known as the hippocampal CA1 area. Their findings, published in Nutritional Neuroscience, suggest that dark chocolate consumption could have beneficial effects on the brain of individuals exhibiting chronic isolation stress. "Although stress causes brain dysfunction, consumption of dark chocolate (DC) has positive effects on brain functions," the researchers wrote in their paper. "The current study investigated the impact of different DC dietary patterns on synaptic potency and plasticity in the hippocampal CA1 area, as well as food intake and body weight in rats under chronic isolation stress." Overall, the experiments carried out by this team of researchers suggest that the systematic consumption of dark chocolate could reverse the adverse effects of chronic isolation stress on the synaptic potency and plasticity of the hippocampal CA1 area. This would in turn have beneficial effects on both memory and learning.   Vitamin C found to block growth of cancer stem cells, says peer reviewed study University of Salford (UK),  July 8, 2022   Increasingly, researchers are discovering the role played by cancer stem cells in the growth and spread of the disease. In groundbreaking new research, vitamin C showed its ability to target cancer stem cells and stop their growth – preventing the recurrence of tumors. In a newly-published study conducted at the University of Salford in Manchester, vitamin C demonstrated its power to stop tumors in their tracks by interfering with cancer stem cell metabolism – suppressing their ability to process energy for survival and growth. The study explored the effects of vitamin C on cancer stem cells – and provided evidence that vitamin C, in the form of ascorbic acid, can target and kill them. The team investigated the impact on cancer stem cells of seven different substances. Three were natural substances, three were experimental drugs, and one was an FDA-approved clinical drug that is widely used. The natural products studied, along with vitamin C, were silibinin – derived from milk thistle seeds – and caffeic acid phenyl ester – or CAPE – derived from honeybee propolis. The experimental drugs were actinonin, FK866 and 2-DG, and the clinical drug was stiripentol. Researchers noted that vitamin C destroyed cancer stem cells by inducing oxidative stress. And, the vitamin performed this process ten times more effectively than 2-DG. By inhibiting glycolysis, vitamin C inhibited mitrochondrial protein synthesis in cancer stem cells – while leaving healthy cells unaffected. All seven of the substances tested inhibited the growth of cancer cells to varying degrees – including the non-toxic natural substances. But researchers said the most “exciting” results were with vitamin C. Again, vitamin C was 1,000 percent more effective than 2-DG, an experimental pharmaceutical drug – in targeting cancer stem cells.      Preterm birth more likely with exposure to phthalates  National Institute of Environmental Health Sciences, July 11 2022 Pregnant women who were exposed to multiple phthalates during pregnancy had an increased risk of preterm birth, according to new research by the National Institutes of Health. Phthalates are chemicals used in personal care products, such as cosmetics, as well as in solvents, detergents, and food packaging. After analyzing data from more than 6,000 pregnant women in the United States, researchers found that women with higher concentrations of several phthalate metabolites in their urine were more likely to deliver their babies preterm, which is delivering three or more weeks before a mother's due date. “Having a preterm birth can be dangerous for both baby and mom, so it is important to identify risk factors that could prevent it,” said Kelly Ferguson, Ph.D., an epidemiologist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, and the senior author on the study published in the journal JAMA Pediatrics. Higher concentrations of most phthalate metabolites examined were associated with slightly higher odds of preterm birth. Exposure to four of the 11 phthalates found in the pregnant women was associated with a 14-16% greater probability of having a preterm birth. The most consistent findings were for exposure to a phthalate that is used commonly in personal care products like nail polish and cosmetics. The researchers also used statistical models to simulate interventions that reduce phthalate exposures. They found that reducing the mixture of phthalate metabolite levels by 50% could prevent preterm births by 12% on average.    Study finds vitamin A directs immune cells to the intestines Purdue University, July 9, 2022 A key set of immune cells that protect the body from infection would be lost without directions provided by vitamin A, according to a recent study. A team of researchers from Purdue University found retinoic acid, a metabolite that comes from digested vitamin A, is necessary for two of the three types of innate immune cells that reside in the intestine to find their proper place. "It is known that vitamin A deficiencies lead to increased susceptibility to disease and low concentrations of immune cells in the mucosal barrier that lines the intestines," said Chang Kim, the professor and section head of microbiology and immunology in Purdue's College of Veterinary Medicine who led the research. "We wanted to find the specific role the vitamin plays in the immune system and how it influences the cells and biological processes. The more we understand the details of how the immune system works, the better we will be able to design treatments for infection, and autoimmune and inflammatory diseases." Within the immune system there are two categories of cells that work together to rid the body of infection: innate immune cells, the innate lymphoid cells and leukocytes that are fast acting and immediately present to eliminate infection; and adaptive immune cells, the T-cells and B-cells that arrive later, but are specific to the pathogen and more effective at killing or neutralizing it. All innate immune cells are produced in the bone marrow, but eventually populate other areas of the body.  Innate lymphoid cells first gather in the lymph nodes before traveling to their final destination, and this is where retinoic acid acts upon two of the three subsets destined for the intestines. Kim and his team found that retinoic acid activates specific receptors in the cells that act as homing devices for the intestines. "It is interesting that both innate and adaptive immune cells share a vitamin A-regulated pathway for migration."   Drinking alcohol while pregnant could have transgenerational effects University of California, Riverside, July 7, 2022 Soon-to-be mothers have heard the warning – don't drink while pregnant.  The  study by Kelly Huffman, psychology professor at the University of California, Riverside, was published in the journal Cerebral Cortex. "Traditionally, prenatal ethanol exposure (PrEE) from maternal consumption of alcohol, was thought to solely impact directly exposed offspring, the embryo or fetus in the womb. However, we now have evidence that the effects of prenatal alcohol exposure could persist transgenerationally and negatively impact the next-generations of offspring who were never exposed to alcohol," Huffman said. To determine whether the abnormalities in brain and behavior from prenatal ethanol exposure would pass transgenerationally, Huffman generated a mouse model of FASD and tested many aspects of brain and behavioral development across three generations. As expected, the first generation, the directly exposed offspring, showed atypical gene expression, abnormal development of the neural network within the neocortex and behavioral deficits. However, the main discovery of the research lies in the subsequent, non-exposed generations of mice. These animals had neurodevelopmental and behavioral problems similar to the those of the first, directly exposed generation. "We found that body weight and brain size were significantly reduced in all generations of PrEE animals when compared to controls; all generations of PrEE mice showed increased anxiety-like, depressive-like behaviors and sensory-motor deficits. By demonstrating the strong transgenerational effects of prenatal ethanol exposure in a mouse model of FASD, we suggest that FASD may be a heritable condition in humans," Huffman said.  

今年３月に東大先進科学機構で独立した北西卓磨さん(@tkitanishi) をゲストに、電気生理 × AAV 黎明期の様子、ノルウェー生活、SPD～スタッフ時代の研究について伺いました。後編に続く（4/27収録） Show Notes(完全版): 北西ラボHP 総合文化研究科先進科学研究機構 岡ノ谷ラボ（現帝京大） 博士の仕事 田代ラボ（現シンガポール） 田代ラボでのお仕事 の筆頭著者レビュー 2005年のオプト論文 PINP論文 (=OptoID or OptoTagging) 田代さんのERCグラント 利根川先生のエングラムの話 Open Ephys Kavli Institute (for Systems Neuroscience) Moserラボ 五十嵐さん 伊藤さん 上村さん 小金澤さん Menno Witterラボ Mor Ther. Generation and Characterization of Chimeric Recombinant AAV Vectors 学振SPD: 学振PD獲得者の中でも特に優れた人が取れるフェローシップ。2020年度に終了。 奥山さん 川島さん 田中さん 松尾ラボ（現・九大） Mayfordのところでのお仕事 Dupretのラボがやってた方向 Claustrumの仕事 Crick and Koch 2005. What is the function of the claustrum? 水関ラボ Subiculumのプロジェクト（水関ラボでのSci Adv） の解説記事（PDF注意） Klausbergerのventral CA1の仕事 256 chのプローブ（所謂Buzsaki256, PDF注意） AAV6が逆行性に感染する…の論文 Editorial notes: ヘッドセットのノイズキャンセリングのせいか、ところどころ音が妙に小さくなってしまいました。すみません。。ただ、お二人にのせられて (?)、いっぱい喋りました。とても楽しい時間でした。ありがとうございました！（北西さん） この収録直後にNeuropixelsデビューしました。とりあえず3本同時記録。実験自体は128chでやってた時とそんな変わらんな〜という感じ。 話の中でもありましたが in vivo自由行動下の電気生理記録ができる国内ラボが本当に増えてきましたね～（宮脇）

Episode 26: This week I'm happy to welcome my longtime friend Heidi Moreau to the show! Tune in for discussions on some of our favorite concerts, dating younger people, partying with rock stars, and why “The Big Show” was such a total nightmare. #Roadway #Trucking #Podcast0:00 - Intro (Lee Michaels)1:19 - Welcome Heidi / Seattle2:50 - Family & Kids8:48 - Mosquito Virus (EEE)11:42 - The Mid 2000's / Music16:18 - Meeting at Roadway23:31 - Drinking24:42 - The Big Show 30:32 - King Cake / Work Party35:43 - The Mariners / Boating40:00 - Rock Star Band-Aids46:49 - Moving to and from Seattle50:16 - Eddie Vedder's 40th52:55 - Maynard & Tool56:57 - Offspring / Green Day / Killers1:05:35 - Quitting Roadway1:16:48 - Michael Jackson1:19:41 - Myspace, FB & IG1:20:40 - Cher / Dating1:28:54 - New Jack Swing1:30:15 - Seattle Bands / DMB1:33:50 - Pot Brownie / The Gorge1:36:52 - Visiting AZ, MI, HI, CA1:39:47 - Outro / Close

In Episode 9 of A Fresh Cup of Fitness, hosts Jessica Danger and Brittany Marsh welcome their first guests. Dr. Adam Schulte is a Family and Sports Physician who has just opened a full-service family medical clinic inside of Resolution CrossFit in Yorba Linda, CA. Dr. Schulte, Owner of Resolution CrossFit Matt Ilharreguy, and members of the coaching staff discuss how they're working to fix the “sick care” system through diet and exercise, incorporating CrossFit and coaching into the medical practice world. If you take one thing from this episode, let it be this: We cannot just keep throwing pills at the problem of healthcare in America. Episode Notes:1:00 -- Resolution CrossFit in Yorba Linda, CA1:16 -- Dr. Adam Schulte, Founder of the Drop-In Doc1:27 -- Coaching Staff at Resolution CrossFit  2:21 -- Introducing the Drop-In Doc on Morning Chalk Up3:01 -- Friendship Fitness in Dublin, OH 3:30 -- How Dr. Schulte first got the idea for the Drop-In Doc5:27 -- Making coaches medical professionals6:50 -- Making diet and exercise major markers in family care7:48 -- Getting away from “Treat em and street em”8:31 -- The “ideal patient”9:14 -- Diet and Exercise should take precedence10:01 -- Why Dr. Schulte knew he needed to be inside an Affiliate11:00 -- Joe Rogan podcast and Ben Greenfield12:15 -- How the coaches at Resolution put this to practice 12:59 -- They think we're “just” coaches15:26 -- C.Y.A in the medical practice world16:48 -- Coaching staff as medical assistants 17:06 -- Incentivizing the coaches 17:36 -- Fixing the broken “sick care” model 18:33 -- Dr. Schulte is open to other coaches and doctors 19:14 -- Accumulating data from and for CrossFitters for multidisciplinary education20:33 -- We get a little geeky on health measurements 21:04 -- Kodi is not overweight, see? 24:17 -- Creating a healthcare network inside the CrossFit space 24:51 -- How the coaching staff at Resolution implements patients diagnosis in the box32:21 -- Exercise Is Medicine: Primary Care Counseling on Aerobic Fitness and Muscle Strengthening 33:06 -- We have to stop throwing pills at the problem36:40 -- Imprinting41:15 -- Reaching out to the Drop-In Doc to replicate in your own affiliate 42:23 -- The CrossFit and Doctor medical portal and HIPAA46:08 -- How to find the Drop-in Doc47:42 -- Other services at the Drop-In Doc48:19 -- Strong Parent, Strong Kids by Shane Trotter49:44 -- Mindset by Carol Dweck Follow Morning Chalk Up: https://www.instagram.com/morningchalkup/. Follow Jessica Danger: https://www.instagram.com/mamadanger/. Follow Brittany Marsh: https://www.instagram.com/the_brittumentary/. Follow The Drop-In Doc: https://www.instagram.com/thedropindoc/ .Email us at: Jessica@morningchalkup.com.