Podcasts about Purkinje

Dr. Kenneth Ellenbogen, Deputy Editor of JACC Clinical Electrophysiology discusses Septal intra-myocardial Purkinje network: a potential new mechanism explaining left bundle branch area pacing physiology.

For today's episode we learn about the cerebellum with Dr. Reza Shadmehr. Dr. Shadmehr is a trailblazing neuroscientist whose groundbreaking work has reshaped our understanding of how the brain controls movement. With a rich academic journey—from a bachelor's in electrical engineering to a PhD in robotics and computer science, followed by a postdoctoral fellowship at MIT—Dr. Shadmehr now leads the Shadmehr Lab at Johns Hopkins University. We dive into his pioneering theories, including motor memory consolidation, state space theory, and the neural encoding of action by the cerebellum's Purkinje cells. The conversation explores the physics of motor movement, prediction, error correction, and the often-overlooked power of the cerebellum—a brain region Dr. Shadmehr calls an “underrated yet powerful” player in our daily lives.Dr. Shadmehr shares his personal path into neuroscience, sparked by a childhood fascination with the brain. This curiosity led him to blend engineering principles with biology, culminating in a lifelong mission to decode how the brain builds internal models for movement. We unpack the cerebellum's critical role in fine-tuning actions—like stopping the tongue precisely or ensuring eye movements hit their mark, to cutting-edge research with marmosets. The episode also touches on the interplay between reward, effort, and cerebellar function, revealing surprising discoveries about how this brain region cancels noise to keep our movements smooth and purposeful. Shadmehr Lab: http://shadmehrlab.orgPublications: http://shadmehrlab.org/publicationsYT Videos (Very Good !): https://www.youtube.com/@shadmehrlab1352Daylight Computer Companyuse "autism" for $25 off athttps://buy.daylightcomputer.com/RYAN03139Chroma Iight Devicesuse "autism" for 10% discount athttps://getchroma.co/?ref=autism00:00 Reza Shadmehr02:26 Daylight Computer Company, use "autism" for $25 discount06:45 Chroma Light Devices- Lights Designed for Humans, use "autism" for 10% discount9:54 Reza's journey into Biomedical Engineering & Neuroscience16:26 Understanding the Cerebellum; 3 primary functions22:07 Neuronal Communication & Purkinje Cells; Sensory and Interneurons25:41 Cerebellum, eyes, and Autistic phenotype; Mesencephalon & other connections28:13 Excitation/Inhibition (E/I) balance; Video examples & Movement deficiencies 29:29 Layers of the Cerebellum34:08 E/I & Brain function36:30 Learning & Memory in the Cerebellum39:54 Dysfunction & Brain Compensation41:57 Basal Ganglia and Cerebellum43:48 Internal Calculators & Prediction49:42 Reward & Movement & Accuracy52:52 Movement control; Eye movements55:56 Purkinje Cells & Tongue movements; deceleration 59:47 Understanding Language of the Cerebellum 1:01:58 Future of Cerebellar Technology X: https://x.com/rps47586YT: https://www.youtube.com/channel/UCGxEzLKXkjppo3nqmpXpzuAemail: info.fromthespectrum@gmail.com

For today's episode, we expand on Autism and Sensory Processing. We return to the mesencephalon—a brainstem region with superior and inferior colliculi—as a critical hub for sensory integration and attention bias. We cover four scientific articles, starting with Marco et al. (2011), which uses EEGs, MEGs, and fMRIs to reveal autism's auditory processing inconsistencies (e.g., delayed N100/M100 cortical responses), tactile hypersensitivity from overactive receptors, and visual processing quirks like reduced fusiform gyrus activation for faces. Russo et al. then explore brainstem-level deficits, showing autistic children's auditory brainstem responses (ABR) to speech syllables like "DA" exhibit poor neural synchrony and phase locking, especially in noise, due to disrupted wave V, A, D, F timing—linking these to language impairments. These findings point to biological roots, including denser neocortical mini-columns (30-40 vs. 50-60 microns in controls) and cerebellar Purkinje cell loss, impairing local processing and long-range connectivity.The episode continues with Leekam et al. (2007), confirming over 90% of autistic individuals have multi-modal sensory abnormalities—hypo- and hypersensitivity tied to serotonin and GABA dysregulation—persisting across life, while Tomchek and Dunn (2007) note 95% prevalence via caregiver reports, hinting at neural pathway disruptions. At some point, we need to acknowledge the mesencephalon's embryological stasis as one of four neural cell types, suggesting its evolutionary role in sensory modulation is key to Autism's biology. These articles collectively highlight altered neural circuitry, from brainstem to cortex, and biases us to remaining within ourselves. Remember, the biology that gives us Autism allows us to be comfortable within ourselves. Marco et al 2011 https://www.nature.com/articles/pr9201193Russo et al 2009 https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1467-7687.2008.00790.xLeekam et al 2007 https://link.springer.com/article/10.1007/s10803-006-0218-7Tomchek & Dunn 2007 https://affectautism.com/wp-content/uploads/2016/05/tomcheck_dunn.pdf0:00 Autism and Sensory Processing; comorbid conditions; Mesencephalon3:03 Article 1 Marco et al 20114:11 Auditory5:00 N100 & M100 tools9:17 Tactile11:23 Visual13:53 Multisensory Integration15:16 Postmortem; Cerebellum & Purkinje Cells; Minicolumns17:06 Speech19:02 Article 2 Russo et al; Brainstem scientists20:28 Auditory Brainstem Response (ABR); Quiet versus Noisy environments; Beatles comparison23:49 Neural Synchrony; Waves V, A, D, F24:33 Phase Locking27:34 Article 3 Leekam et al 2007; Neuroplasticity33:09 Article 4 Tomchek & Dunn 200736:36 Reviews/Ratings and Contact InfoX: https://x.com/rps47586Hopp: https://www.hopp.bio/fromthespectrumYT: https://www.youtube.com/channel/UCGxEzLKXkjppo3nqmpXpzuAemail: info.fromthespectrum@gmail.com

Dr. Giorgia Quadrato is Assistant Professor of Stem Cell and Regenerative Medicine at the University of Southern California. Her research focuses on brain developmental and neural organoids. She talks about protocols for generating cerebellar organoids, including those with functional Purkinje cells. She also discusses a transcriptomic atlas of neural organoids and the stem cell research landscape in California.

Autoimmune neurology is a rapidly evolving subspecialty that focuses on neurologic disorders with atypical immune responses. In this episode, Aaron Berkowitz, MD, PhD FAAN, speaks with Sean J. Pittock, MD, an author of the article “Overview and Diagnostic Approach in Autoimmune Neurology,” in the Continuum August 2024 Autoimmune Neurology issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Pittock is the director for the Center for Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Overview and Diagnostic Approach in Autoimmune Neurology Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Transcript Full transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.    Dr Berkowitz: This is Dr Aaron Berkowitz, and today, I'm interviewing Dr Sean Pittock about his article, “Introduction to Autoimmune Neurology and Diagnostic Approach”, which he wrote with his colleague, Dr Andrew McKeon. This article is a part of the August 2024 Continuum issue on autoimmune neurology. Welcome to the podcast, Dr Pittock. Could you introduce yourself to our audience?    Dr Pittock: Well, thank you very much, Dr Berkowitz. So, yeah, I'm a neurologist at the Mayo Clinic. I direct the neuroimmunology laboratory with Dr McKeon and Dr Mills here, and I have also been very much involved in the autoimmune neurology section at the American Academy of Neurology.    Dr Berkowitz: So, many of you probably know Dr Pittock - or if you don't know, you've certainly diagnosed diseases that he has described and written about, and so it's a real honor to get to talk to you today and pick your brain a little bit about some of these complex diseases. So, autoimmune neurology is certainly one of the most exciting subspecialties of our field. I feel like when I talk to students and they ask me to make a case for why they should consider neurology as a career, I tell them, “Of course, I have many reasons I love neurology”, but one thing I mention is that, although many other fields of medicine may have made incredible advances as far as treatments, I can't think of too many other fields outside neurology where entirely new diseases have been described since I've been in training and come out of training - and many of those have been in your field of autoimmune neurology. I can think of cases where I've heard you or one of your colleagues on a neurology podcast describing a new antibody, new disease, and a few weeks later, we see that disease and give a patient a diagnosis that had been elusive from other physicians and hospitals. It's a very exciting, gratifying area. It's also daunting, like, every time I go to the AAN and hear one of your colleagues, there's a new disease, and we realize, “Oops! Was I missing that?” or, “Am I going to see this?” And so, hoping to pick your brain a bit today about some of the key concepts and how to keep them in mind so our listeners can recognize, diagnose, and treat these conditions, even if they can't remember every single antibody in your article and all the new ones you and your colleagues will probably discover between now and when this, um, podcast is released. So, before we get into some of the important clinical aspects of these conditions, could you just lay out sort of the broad breaststrokes, the lay of the land of cell-mediated versus antibody-mediated paraneoplastic versus nonparaneoplastic cell surface versus intracellular - how can we sort of organize this area in our minds?    Dr Pittock: Yeah. It's complex, and it's really an evolving story. But the importance, really, from the perspective of the reader and the perspective of the clinician is that we're talking about disorders where we can actually do something - we can actually impact patients.  And we think about the concept of stopping and restoring in neurology now. We're talking about disorders where we have the potential to stop these inflammatory immune-mediated disorders and, potentially, by stopping early, we may be able to restore function - so, a really important new and evolving field in neurology, because you don't want to miss these conditions. Trying to get your head around the complexity of these entities is difficult, but what we've done in this chapter is, really, to try and lay the groundwork for the following chapters, but provide somewhat of a simplistic approach, but a practical approach that really, I think, can help clinicians. So, the way I think of it, a lot of autoimmune neurology really has stemmed from the discovery of antibodies that cause neurological disease, and the examples of those would be going back to myasthenia gravis (with antibodies to the acetylcholine receptor), going back to Lambert-Eaton syndrome. And then, you know, even if you go back to the older traditional paraneoplastic disorders (the Hu, the Ri, the Yo), at the end of the day, you really have two essential entities, if you want to be very simple. The first is disorders that are caused by an antibody, and the second are disorders where the antibodies you detect are not causing the disorder, but they're telling you that there's predominantly a cellular or T-cell mediated attack of the nervous system. And I think thinking about the diseases in those kind of simple terms helps us when we think about what would be the best treatment to use in these types of cases.   Dr Berkowitz: Fantastic. I think that's very helpful. And just to make sure it's clear in the minds of our listeners when we're dividing into these sort of causative antibodies versus antibodies that might be, uh (I don't know if I'm using the word properly), but, sort of epiphenomena (or they're present, but they're not causative) as you said, can you just give some examples of the ones on either side and how making this distinction helps us in practice?    Dr Pittock: Yes. So, antibodies that are causative of disease - I think, you know, the one that I've done a lot of work on is in neuromyelitis optica, where you have antibodies that are targeting a water channel that sits on an astrocyte, and so it causes NMOSD, or what we consider an autoimmune astrocytopathy. And we know that when the antibody binds to the target, many things can happen. So, when aquaporin-4 antibodies bind to aquaporin-4, they can do a lot of things. They can cause internalization, they can activate complement that results in the killing of the cell - but there can be other situations. For example, when NMDA-receptor antibodies bind to the NMDA receptor, then a variety of different things can occur different to water channel autoimmunity - where, for example, the receptor (the NMDA receptor) is downregulated off the cell surface, and that results, to some extent, in the neuropsychiatric phenomenon that we see in NMDA-receptor autoimmunity. And, obviously, when you have a situation where the antibodies are causing the disease, removal of those antibodies, or the reduction in the production of those antibodies, is going to help patients. Now, on the other side, we have antibodies that we detect in the blood or in the spinal fluid, and those antibodies are targeting proteins that are inside the cell - so those antibodies we don't consider as being pathogenic. Now, remember, there are sometimes situations where proteins that are inside the cell occasionally can be available for antibodies to bind at certain situations. So, for example, in the synapse, amphiphysin or the septins, may at times become available. And so, sometimes, there are targets or antibodies that are somewhat in between those two simplistic concepts. But when we're talking about antibodies that are targeting proteins on the inside of the cell, remember that antibodies don't just suddenly occur. There's a whole process of presentation of target antigen at the lymph node, and then both a T- and a B-cell response. The B-cell response potentially produces the antibodies but also triggers and stimulates T-cells, and those T-cells then go on to cause the disease. And those T-cells are very problematic, because those classical paraneoplastic and the newer ones we've described (and many have described) - these are associated with quite severe neurological disability, and they're very, very difficult to treat. And if you ask me, “Where is the holy grail of autoimmune neurology therapeutic research?” It's in trying to actually figure out ways of treating the predominantly T-cell mediated paraneoplastic and autoimmune neurological disorders. We're making great headway in terms of the treatments of the antibody-mediated neurological disorders.   Dr Berkowitz: That's a helpful overview. So, sticking with this framework, you mentioned as sort of the “causative antibody” category and the antibodies that are predominantly for intracellular antigens, but not believed to be causative - I want to make sure I'm understanding this correctly and we can convey it to our listeners - I believe you said in your paper, then, that the antibodies that are predominantly causative are more likely to be associated with conditions that are very treatable, as compared to the intracellular antibodies that are not thought to be causative, as you just said the disability can be irrecoverable or very hard to treat. And I believe another theme in your paper that you brought out is the antibodies that tend to be causative tend to be cell surface and tend to be less likely to be associated with underlying cancer (although not a perfect rule), and the intracellular antigens more commonly associated with cancer in those cases to look very hard for a cancer before giving up. Are those themes that I understand them from your paper properly, or anything else to add there?    Dr Pittock: Yes, I think that that's exactly the message that we were trying to get across, so that's good news that you've picked up on the themes. I think, yeah, in simple terms, remember that when a cytotoxic T-cell identifies the peptide that its T-cell receptor will target, the ultimate outcome is poor, all right? T-cells are like the marines - they don't mess around. Once they find their target, they eliminate that target, and so, it's really difficult to treat those types of diseases if you get them late. And most patients with cytotoxic T-cell mediated paraneoplastic neurological disorders, oftentimes, by the time they get to a center of excellence, the boat has left the dock in many respects - in other words, it's too late. So, you know, I will often see patients, for example, with progressive cerebellar degeneration (say, in the context of Purkinje cell autoantibody type 1 antibodies and a breast cancer), and if those patients are in a wheelchair at the time that I see them, there's very, very little that we can do. So, you really want to try and get that patient into the office, you know, when they're using a cane (or not), and then, potentially, you have the opportunity - using very aggressive immunosuppressive medications - to make a difference. And that is quite different to other scenarios, where, for example, if you have NMDA-receptor encephalitis - as many of the readers will know, this is a condition that is very treatable, and most patients do very well, because the antibodies, they're disrupting function, but they're not killing the neuron, as we see in those more aggressive, paraneoplastic cytotoxic T-cell mediated diseases.   Dr Berkowitz: Also, in terms of searching for an underlying cancer, another theme in your paper as I understood (but want to make sure I'm understanding and conveying to our listeners and hear your thoughts), that the cell surface and treatable antibody-mediated syndromes, as you mentioned (NMO, NMDA) tend to be less associated with underlying cancers (although can be), whereas the intracellular antigens, um, a much higher percentage of those patients are going to end up having underlying cancers. Is that correct, or any notable exceptions to be aware of in that framework?    Dr Pittock: Yeah, I think the major exception to the rule for the antibodies that are targeting intracellular antigens is the GAD65 antibody story. We generally don't consider the stiff person syndrome, cerebellar ataxia, or other autoimmune neurological disorders associated with very high levels of GAD65 antibodies - those are generally not paraneoplastic. And then there are always exceptions on both sides. You know, one of the benefits of understanding the implications of certain antibodies is trying to understand, you know, what is the likelihood of identifying a malignancy, which antibodies are high-risk antibodies (in other words, high-risk paraneoplastological disorders), and which are low risk in terms of cancer? And, you know, age and the demographic of the individual is often important, because we know, for example, with NMDA-receptor antibodies, the frequency of ovarian teratoma varies with the age of the patient.   Dr Berkowitz: Fantastic. And we encourage our listeners to read your articles – certainly, some very helpful tables and figures that help to elucidate some of these broad distinctions Dr Pittock is making - but just to summarize for the antibody-related part of autoimmune neurology, we have one category of cell-surface antibodies and another of intracellular antibodies. Both can cause very severe and varied neurologic presentations, but the cell surface tend to be more treatable, less likely to be associated with the underlying cancer, and the intracellular less treatable, more likely to be associated with the underlying cancer - but, as with everything in neurology and medicine, exceptions on both sides. Is that a fair aerial view of some of the details we've discussed so far, Dr Pittock?    Dr Pittock: Yeah, I think so. I mean, I also think that, you know, not only, at least, for the antibody-mediated disorders (you know, as we discussed) we have drugs that will reduce the production of those antibodies, but we're also learning a lot more about the cytokine and chemokine signatures of these disorders. For example, NMO, water-channel antibody-mediated diseases are associated with elevated levels of IL-6. We know, for example, in LGI1 encephalitis and other encephalitides, that IL-6 also is elevated at the time of that encephalitic process. And so, the potential to target IL-6 with, you know, drugs that inhibit IL-6 and the IL-6 receptor, these potentially have, you know, a role to play in the management of these types of patients - whereas in the T-cell mediated disorders, you know, no advance has been made in the treatment of those conditions, I would say, in over 50 years. So, for example, the standard of treatment is steroids and then drugs that impact the bone marrow, and so we really haven't moved forward in that respect. And that, I think, is an area that really needs drive and enthusiastic out-of-the-box thinking so that we can try to get better treatments for those patients.   Dr Berkowitz: This has been a helpful overview. I look to dive into some of the scenarios that frontline practitioners will be facing thinking about these diseases. An important point you make in your article is that autoimmune and antibody-mediated neurologic syndromes can affect any level of the neuraxis. Even just our discussion so far, you've talked about anti-NMDA receptor encephalitis, you've talked about myasthenia gravis (that's at the neuromuscular junction), you've talked about paraneoplastic cerebellar degeneration - there can be an “itis” of any of our neurologic structures and that “itis” can be antibody-mediated. So, one of the key messages you give us is, one, that these are sort of in the differential diagnosis for any presenting neurologic syndrome, and, two, sort of one of the key features of the history, really, to keep in mind (since we could be anywhere along the neuraxis) is the subacute presentation when this should really sort of be top of mind in our differential diagnosis - so, many of these patients are going to be mystery cases at the outset. And one striking element you bring out in the paper is that, sometimes, the MRI, CSF, electrophysiology studies may be normal or nonspecifically abnormal, and although it's very helpful when we can send these antibody panels out, in some cases, resources are limited or institutions have certain thresholds before you can send these out (because neurologists love to send them in). Sometimes, they are not necessarily appropriate. So, love to hear your thoughts on when we should be sending these panels. What are some clues? Um we have a subacute neurologic presentation at any level of the neuraxis, and when it's not anti-NMDA receptor encephalitis, that is sort of a clear phenotype in many cases. How you would approach a patient, maybe, where the MRI is either normal or borderline abnormal (or people are squinting at the medial temporal lobe and saying, “Maybe they're a little brighter than normal”), CSF is maybe normal or nonspecifically, um, and the protein is a little high, but no cells? What clues do you use to say, you know, “These are the patients where we should be digging deep into antibody panels and making sure these are sent and not miss this diagnosis?”    Dr Pittock: Well, thank you. That's a good question. So, I think, you know, first of all, these are complex cases. So, the patient is sitting in front of you and you're trying to figure out, first of all, Is this a hardware or a software problem? Are we definitively dealing with an encephalitis or an organic neurological entity that's immune-mediated? And, you know, the way I think of it is, for me, you see a patient, it's a twenty-five-piece jigsaw puzzle and you've got two pieces, and you're trying to say, “Well, if I step back and look at those two pieces, do I have any sense of where we're going with this patient?” So, the first thing you need to do is to collect data, both the clinical story that the patient tells you (and I think you make the good point that that subacute onset is really a big clue), but subacute onset, also fluctuating course, sometimes, can be important. The history of the patient - you know, Is the patient somebody who has a known history of autoimmune disease? Because we know that patients that have thyroid autoimmunity are more likely to have diabetes, they're more likely to have gastrointestinal motility or dysmotility, they're more likely to have a variety of different immune-mediated conditions. So, is there a family history or a personal history of autoimmunity? Is the patient at high risk for malignancy? Are there clues that this potentially could be a tumor-initiated immune process affecting the nervous system? The neurological exam also is extremely important because, again, that helps you, first of all, kind of define and get some objectivity around what you're dealing with. So, does the patient have hyperreflexia? Are there signs that there is neurological involvement? And then, really, what I think we need to do is to try and frame the predominant neurological presentation. So, what is the major issue? Because a lot of these patients will have multiple complaints, multiple symptoms, and it's very important to try and identify the major presentation. And that's important, because the neural autoantibody tests are now presentation-defined - in other words, they're built around the neurological presentation, because the old approach of just doing, apparently, a plastic evaluation is gone, because we've got to a stage where we have now so many neural antibodies, you can't test every single neural antibody. So, if you're suspecting that there may be an autoimmune neurological component, then you really need to think about what would be the most appropriate comprehensive evaluation I need to do for this patient. So, for example, if a patient comes in with a subacute-onset encephalopathy, you're probably going to want the autoimmune encephalitis evaluation, and then you have to pick whether it's going to be serum or spinal fluid - and as we outlined in the paper, there are certain antibodies that are better detected in serum versus spinal fluid. So, for example, in adults over the age of 50, LGI1 is much more accurately detected in serum than spinal fluid, and the absolute opposite is true for NMDA-receptor antibody detection. One of the most important components of the neurological evaluation is the spinal fluid, but actually looking at the white cell count - and in fact, sometimes, it's quite interesting to me that I'll often see patients referred with a diagnosis of encephalitis and autoimmune encephalitis, and yet they haven't had a spinal fluid examination. So, the presence of a white cell count, you know, greater than five is hugely helpful - it's like two pieces of that twenty-five-piece jigsaw, because that really tells you that there is something inflammatory going on. And now, in terms of imaging, you're right - some patients will have normal MRI. And if you really do think that there's evidence of - you know, for example, you do an MRI, but you're getting a good sense that there's a temporal lobe seizure occurring, MRI looks normal, the EEG shows some abnormalities in the mesial temporal area - you know, considering additional imaging modalities (like PET scan of the brain), I think, is reasonable. We know that in NMDA-receptor encephalitis cases, 30% of patients will have normal MRI but they'll often have abnormalities on the PET scans. So, I think, what we do is we try to gather data and gather information that allows us to add in pieces of that jigsaw so that, eventually, after we've done this evaluation, we can see now we have ten pieces. If we step back, we say, “Yes, now we know what this condition is”, and then we essentially plan out the therapeutic approach dependent on what we've found. In terms of identification of underlying malignancy, you know, different people have different approaches. Our approach generally has been to try to get a PET-CT scan of the body as our first go-to test, because, actually, we found that CT chest abdomen and pelvis really actually delivers the same amount of radiation - and from a cost perspective, it's about the same - and we have found that PET-CTs really do provide a higher sensitivity for cancer detection.   Dr Berkowitz: Perfect. A lot of very helpful clinical pearls there. So, in closing, Dr Pittock, I've learned a lot from you today. I'm sure our listeners will as well. What does the future hold in this field? What's coming down the pipeline? What are we going to be learning from you and your colleagues that are going to help us take care of patients with these diseases going forward?    Dr Pittock: Well, thank you, Dr Berkowitz, for that question. I think the future is very bright and very exciting, and, hopefully, some of the more junior members will be enthused by this Continuum series, and, hopefully, we'll go into this area. So, let's talk about the future. The future, I think, is going to be of great interest. Firstly, there's going to be continued discovery of novel biomarkers, and the reasons for that is because of the technical and technological advances we've seen. So, for example, there have been many, many antibodies discovered by us and others that have been discovered on the basis of, for example, phage technology. In fact, the Kelch 11 biomarker discovery in collaboration with UCSF and our group was done on the basis of Joe DeRisi and Michael Wilson's phage approach. And we're actually using that now at Mayo Clinic, and we've discovered about three or four new antibodies just in the last couple of years using this technology (and that here is led by John Mills and Div Dubey). And then, we're also going to see, I think, the evolution of protoarrays much more in biomarker discovery, so, we'll have more antibodies, and again, I think, generally, those antibodies will fall into the two categories we kind of described - so, you know, in terms of the approach to those conditions, maybe not so much change. I do think, though, that the introduction and the utility of comprehensive cytokine and chemokine analysis in the future will assist us in making diagnoses of seronegative encephalitis, but also potentially will direct therapy. So, for example, cytokine A is elevated - maybe that would be a potential target for therapy that's available for these patients with rare and potentially very disabling disorders. Then, when we look at the cytotoxic T-cell mediated disorders, I think the major areas of advance are going to be in better understanding the immunophenotype of cytotoxic T-cell mediated diseases, and then the potential development of tolerization strategies using the specific targets, those specific epitope targets that are involved in paraneoplastic and nonparaneoplastic diseases, and seeing if we can vaccinate patients, but move that immune response into more of a tolerogenic immune response rather than a cytotoxic killing response. And then I think, lastly, we're going to see a dramatic revolution in CAR-T therapeutic approaches to these types of disorders moving forward - and not just, you know, CAR-T therapies that are targeting, you know, CD19 or CD20, but CAR-Ts that are actually personalized and developed so that they can target the specific B- and T-cells in an individual patient and actually do a very fine removal of that autoimmune pathologic process that I think would have significant benefit for patients not only in stopping progression, but also in significantly reducing the potential of side effects - so, a much more targeted approach. So, that's where I think the next ten years is going to be. I think it's very exciting. It's going to require the collaboration of neurologists with, you know, immunologists, hematologists, you know, across the board. So, a very exciting future, I think, for this field.    Dr Berkowitz: Exciting, indeed. And we have learned so much from you and your colleagues at the Mayo Clinic about these conditions, and I definitely encourage our listeners to read your article on this phenomenal issue that really gives us a modern, up-to-date overview of this field and what's coming down the pipeline. So, a real honor to get to speak with you, pick your brain about some of the clinical elements, pitfalls and challenges, and also hear about some of the exciting signs. Thank you so much, Dr Pittock, for joining me today on Continuum Audio.   Dr Pittock: Thank you very much.    Dr Berkowitz: Again, today, I've been interviewing Dr Sean Pittock, whose article with Dr Andrew McKeon on an introduction to autoimmune neurology and diagnostic approach appears in the most recent issue of Continuum on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thank you so much to our listeners for joining us today.    Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/audioCME. Thank you for listening to Continuum Audio.

William H. Sauer, MD, FHRS, CCDS, Brigham and Women's Hospital is joined by Andrés Felipe Miranda-Arboleda, MD, Brigham and Women's Hospital Babak Nazer, MD, University of Washington to discuss how Purkinje fibers play an important role in the initiation and maintenance of ventricular fibrillation (VF) and polymorphic ventricular tachycardia (PMVT). Fascicular substrate modification (FSM) approaches have been suggested to treat recurrent VF in case reports and small case series. https://www.hrsonline.org/education/TheLead https://www.jacc.org/doi/10.1016/j.jacep.2024.03.035 Host Disclosure(s): W. Sauer: Honoraria/Speaking/Consulting: Biotronik, Biosense Webster, Inc., Abbott, Boston Scientific, Research: Medtronic   Contributor Disclosure(s): A. Miranda-Arboleda: Nothing to disclose. B. Nazar: Honoraria/Speaking/Consulting: Biosense Webster, Boston Scientific, Edwards Lifesciences, Research: Biosense Webster

On this episode we have some Astronomer friends on to discuss our thoughts from the Total Solar Eclipse! Matt Schricker (@Bostronomy), Andrew Abban (@aa.astro01), and Thorne Ransom (@ransomobservatory) join us to share their Astronomy Origin Stories and their experience during the Total Solar Eclipe. For some it was our first, and others were looking for redemption from 2017. But all of us were close to speechless when it happened, until we had this mega podcast for some Eclipse Talk. Maine was one of the best places in the country to see the Total Solar Eclipse, given the cloud coverage on the day of the eclipse. Even us New Englanders were shocked that out of the 13 states in the US - Maine would be the place to be. But, as you'll hear and see from the images taken...we had the best seats in the solar system that day! Thank you to our guests and new friends for such a fun Eclipse Talk - make sure to follow them online for awesome astrophotography! Let us know if you were able to watch the total solar eclipse and whether it was your first! We'd love to hear from you. Email us at todayinspacepodcast@gmail.com Topics from the episode: eclipse, telescope, astronomy, friend, crazy, mind-blowing, pictures, Maine, years, night, shadow, sky, totality, mountain, total solar eclipse SOURCES: What is a Meridian Flip? https://www.cloudynights.com/topic/236513-meridian-flip/ What is a Meridian Flip when using a Telescope? https://www.youtube.com/watch?v=xnktqwTwCMA The 'Topics from the episode' above and the timestamps below for the episode were generated using AI (otter.ai) by processing the audio file. Timestamps: 00:00 Eclipse Talk w/ 3 Astronomers 05:03 Astronomy Origin stories w/ Andrew & Thorne  10:38 The Journey to Maine, and the challenge of chasing good Total Eclipse weather 15:02 REACTIONS to the Total Solar Eclipse  23:01 Astronomy Trio's experience during the Eclipse.  28:04 Astrophotography techniques and tools used during the total solar eclipse.  37:53 Road trips, traffic, and big dogs dangerously close to telescopes 42:12 The Purkinje effect with colors during the Total Solar Eclipse 47:03 The time and science of Solar Eclipse viewing 52:48 Astronomy and Starparties 59:11 The impact & human experience of the solar eclipse 01:14:16 Astrophotography, equipment, and friends ----------------- Here's to building a fantastic future - and continued progress in Space (and humanity)! Spread Love, Spread Science Alex G. Orphanos We'd like to thank our sponsors: AG3D Printing Magic Mind (magicmind.com use code TODAYINSPACE20 for 20% OFF or up to 56% off subscription) Follow us: @todayinspacepod on Instagram/Twitter @todayinspace on TikTok /TodayInSpacePodcast on Facebook  Support the podcast: MAGIC MIND (magicmind.com/learn) AND use my code: TODAYINSPACE20 More ways to support us: • Buy a 3D printed gift from our shop - ag3dprinting.etsy.com • Get a free quote on your next 3D printing project at ag3d-printing.com • Donate at todayinspace.net #space #rocket #podcast #people #spacex #moon #science #3dprinting #nasa #tothemoon #spacetravel #spaceexploration #solarsystem #spacecraft #technology #vaonis #vespera #hestia #telescope #aerospace #spacetechnology #engineer #stem #artemis #lunar #totalsolareclipse  

CNN online article: Wear red and green to experience the Purkinje effect during the total solar eclipsePlease find more information to each episode on the Chromosphere website.

Amanda Riffo hlaut á dögunum íslensku myndlistarverðlaunin fyrir sýningu sína House of Purkinje í Nýlistasafninu, sýningarstjóri var Sunna Ástþórsdóttir. Amanda er frönsk-sílesk myndlistarkona sem hefur verið búsett í Reykjavík í rúman áratug. Hún ólst að hluta til upp í franskri sveit en fluttist snemma á lífsleiðinni með fjölskyldu sinni til Parísar. Myndlist lék ekki ýkja stórt hlutverk í uppeldi hennar en heimsóknir á söfn og gallerí í París voru tíðar og í raun venjubundnar hjá fjölskyldu hennar. Hún nam við Háskóla hinna fögru lista í París en sá skóli bauð á námsárum hennar upp á ótrúlegt frelsi fyrir nemendur sína sem krafðist þess að þeir skipulögðu sig sjálfir eða flosnuðu upp úr námi. Amanda segist hafa flutt til Íslands fyrir slysni, en hugmyndin að koma hingað í listamannadvöl kviknaði eftir að hún fór á litla íslenska tónlistarhátíð í París um 2007. Hún ætlaði að vera hér í nokkra mánuði en tíminn hljóp frá henni. Samkvæmt dómnefnd myndlistaverðlaunanna: Á sýningunni House of Purkinje samstillir Amanda ólíkar frásagnir á afar snjallan hátt, allt frá þekkingarfræði og ljósfræði, í gegnum eigin reynslu sína af listtengdu bútasaums-hagkerfi til gagnrýnnar skynjunar á samtímalistinni og gangverki þess. Það er mat dómnefndar að House of Purkinje sé einstaklega áhugaverð sýning sem virðist í upphafi vera hlé á uppsetningarferli sýningar á meðan hvert smáatriði í glundroða slíkra ferla er listaverk, sem endurspeglar á snjallan hátt vinnusiðferði innan listheimsins og skapar breyttan veruleika þar sem hver hlutur er sviðsett útgáfa af sjálfum sér, rétt eins og á kvikmyndasetti.

Artist Amanda Riffo joins us to discuss newly receiving the 2024 Icelandic Art Prize Artist of the Year award, exhibitions, projects, residencies and creative coincidences. Amanda received the award based on her exhibition House of Purkinje, her first major solo show, which was exhibited in The Living Art Museum in 2023 and curated by Sunna Ástþórsdóttir. Amanda's natural storytelling takes us through various works and exhibitions, art encounters, soundtracks, some of her personal history and the ways she approaches thinking about and creating art. Amanda Riffo (b.1977) is a French-Chilean artist based in Reykjavik. After completing a Master of Arts at the École Nationale Supérieure des Beaux-Arts, Paris, she later participated in exchange programs in Tokyo and Beirut. Her work has been shown in Europe, Japan, Iceland, Chile, Finland, Belgium and more. Exhibition projects in Iceland include her solo exhibition in Open (2018) and Skaftfell (Seyðisfjörður, 2019), as well as participation in the international art biennial Sequences Xl (2019). She is the current recipient of the Artist of the Year, Icelandic Art Prize and the Friend of Nýlo Artist for 2024. Amanda Riffo - House of Purkinje at the Living Art Museum  @amanda_riffo @nylistasafnid @icelandic_art_prize @gallery_port The episode's playlist by Amanda Riffo herself: * James Ferraro -individualism-album Human History 3 /2016** Robert Wyatt -at last I am free-album Nothing Can Stop Us /1982*** Ol dirty Bastard -Brooklyn Zoo -/1995

Talk to text. The Purkinje effect. Making sausage. Not hotdogs. Grilled cheese tomato soup. Hidden Valley launches new ranch flavors. 5 mistakes that get us hacked. Cereal Day! Jokes with Chelsea.

Nap time. Talk to text. The Purkinje effect. Making sausage. Not hotdogs. Grilled cheese tomato soup. Hidden Valley launches new ranch flavors. 5 mistakes that get us hacked. Cereal Day! Jokes with Chelsea. Miami Beach is trying to break up with spring break. Red Bull.

Artist and project manager of the Icelandic Art Prize Tinna Guðmundsdóttir joins us to discuss the nominations for the 2024 Icelandic Art Prize. In this overview episode, we detour from our usual format, and take some time to review the artists, and the exhibitions, that are nominated for the Prize's two main award categories; Artist of the Year & Motivational Award.    The Icelandic Art Prize awards, including the Artist of the Year award, the Motivational Award, Publication of the Year, Group exhibition of the Year and Honorary Artist of the Year, annually award outstanding visual artists, as well as encouraging new artistic creations, and recognizing significant contributions made to the field of contemporary art over the year. The award ceremony will be held on March 14 at Iðnó, where the Icelandic Love Corporation and artist Pola Sutryck will contribute to the evening's festivities. The nominees for the two award categories are:  Artist of the Year Nominations Amanda Riffo - House of Purkinje at the Living Art Museum Arnar Ásgeirsson - Cleaning Methods at the Neskirkja Church Geirþrúður Finnbogadóttir Hjörvar - Index at Ásmundarsalur Ólöf Nordal - Blird at Ásmundarsalur @olof_nordal Motivational Award Nominations Almar Steinn Almarsson - Almar in the Tent at Svavar Guðnason Art Museum  Brák Jónsdóttir - Possible Oddkin at the Nordic House Sara Björg Bjarnadóttir - Two infinities betwen 1 and 3 at Akureyri Art Museum // Created and produced by the Icelandic Art Center, Out There brings co-hosts Becky Forsythe @beforsythe and Þórhildur Tinna Sigurðardóttir @tindilfaetta in conversation with artists, curators and art professionals.

Fri, 16 Feb 2024 21:15:00 GMT http://relay.fm/rd/228 http://relay.fm/rd/228 Big Filter Boy 228 Merlin Mann and John Siracusa John has Follow-Up on the Ides of March that leads to an examination of Roman numerals, contextual adjectives, and the challenge of adapting software for the peoples of Volapük. John has Follow-Up on the Ides of March that leads to an examination of Roman numerals, contextual adjectives, and the challenge of adapting software for the peoples of Volapük. clean 5653 Subtitle: I never said she stole my money.John has Follow-Up on the Ides of March that leads to an examination of Roman numerals, contextual adjectives, and the challenge of adapting software for the peoples of Volapük. This episode of Reconcilable Differences is sponsored by: Squarespace: Save 10% off your first purchase of a website or domain using code DIFFS. Links and Show Notes: John has Follow-Up on the Ides of March that leads to an examination of Roman numerals, contextual adjectives, and the challenge of adapting software for the peoples of Volapük. Next up is some guidance on the rope John was trying to push in the previous episode, and Merlin expresses gratitude to the listeners who also didn't know Aja has a person on it. Your hosts learn that you can't make an Omelas without…you know. Breaking something. Then, John and Merlin talk about the American singer, Taylor Swift. Apparently still in Follow-Up, there's more talk about DisneySea, and then Merlin gets surprisingly animated in discussing his ardor for some networking software and a recent music video. Finally, the listener is treated to a discussion of sports in movies. For this month's members-only bonus show, John has questions about Merlin's AI friends. You can sign up today to hear all the member episodes, get more bonus stuff, and, yes, support our program. (Recorded on Tuesday, February 6, 2024) Credits Audio Editor: Jim Metzendorf Admin Assistance: Kerry Provenzano Music: Merlin Mann The Suits: Stephen Hackett, Myke Hurley Get an ad-free version of the show, plus a monthly extended episode. The Ides of March "I never said she stole my money." - One Sentence With 7 Meanings Pushin' a Rock - America's Funniest Home Videos The Young Ones - "Nozin' Aroun'" - YouTube "Knifin' Around" with Thom Yorke - YouTube Yoshimi Battles the Pink Robots - The Flaming Lips Clouds Taste Metallic - The Flaming Lips Chris Williams on the Aja cover - Mastodon Merlin on the Aja cover - Mastodon WPIX channel 11 NY logos Volapük XLIFF "Ones Who Walk Away From Omelas” by Ursula K LeGuin Why Don't We Just Kill the Kid In the Omelas Hole? Taylor Swift - "Change" (2008) - YouTube Taylor Swift - "Mean" (2011) - YouTube Bleachers - "Tiny Moves" - YouTube Kenzo World - YouTubeMargaret Qualley dances her little heart out in this outstanding commercial directed by Spike Jonze. Kenzo World Mirror Shot Breakdown - YouTube @RecDiffs on Mastodon Tokyo DisneySea Review: Simply Incredible - YouTube Sindbad's Storybook Voyage: Tokyo DisneySea's Hidden Gem - YouTube Mystic Manor at Hong Kong Disneyland 2016 - YouTube Maid - Netflix All Too Well: The Short Film - YouTube Go Away Green - Wikipedia"or no-see-um-green" Discover Disney's Color Magic With Go Away Green and Blending Blue! - Inside the Magic Walt Disney World Best Kept Secrets - Magic KingdomListen for the subtle music changes between lands in the MK. Also notice how the pavement changes as well, especially as you travel across the nation and through time from Liberty Square (the Colonial Eastern US) into the Frontierland (western US).  Purkinje effect - WikipediaThe Purkinje effect occurs at the transition between primary use of the photopic (cone-based) and scotopic (rod-based) systems, that is, in the mesopic state: as intensity dims, the rods take over, and before color disappears completely, it shifts towards the

Fri, 16 Feb 2024 21:15:00 GMT http://relay.fm/rd/228 http://relay.fm/rd/228 Merlin Mann and John Siracusa John has Follow-Up on the Ides of March that leads to an examination of Roman numerals, contextual adjectives, and the challenge of adapting software for the peoples of Volapük. John has Follow-Up on the Ides of March that leads to an examination of Roman numerals, contextual adjectives, and the challenge of adapting software for the peoples of Volapük. clean 5653 Subtitle: I never said she stole my money.John has Follow-Up on the Ides of March that leads to an examination of Roman numerals, contextual adjectives, and the challenge of adapting software for the peoples of Volapük. This episode of Reconcilable Differences is sponsored by: Squarespace: Save 10% off your first purchase of a website or domain using code DIFFS. Links and Show Notes: John has Follow-Up on the Ides of March that leads to an examination of Roman numerals, contextual adjectives, and the challenge of adapting software for the peoples of Volapük. Next up is some guidance on the rope John was trying to push in the previous episode, and Merlin expresses gratitude to the listeners who also didn't know Aja has a person on it. Your hosts learn that you can't make an Omelas without…you know. Breaking something. Then, John and Merlin talk about the American singer, Taylor Swift. Apparently still in Follow-Up, there's more talk about DisneySea, and then Merlin gets surprisingly animated in discussing his ardor for some networking software and a recent music video. Finally, the listener is treated to a discussion of sports in movies. For this month's members-only bonus show, John has questions about Merlin's AI friends. You can sign up today to hear all the member episodes, get more bonus stuff, and, yes, support our program. (Recorded on Tuesday, February 6, 2024) Credits Audio Editor: Jim Metzendorf Admin Assistance: Kerry Provenzano Music: Merlin Mann The Suits: Stephen Hackett, Myke Hurley Get an ad-free version of the show, plus a monthly extended episode. The Ides of March "I never said she stole my money." - One Sentence With 7 Meanings Pushin' a Rock - America's Funniest Home Videos The Young Ones - "Nozin' Aroun'" - YouTube "Knifin' Around" with Thom Yorke - YouTube Yoshimi Battles the Pink Robots - The Flaming Lips Clouds Taste Metallic - The Flaming Lips Chris Williams on the Aja cover - Mastodon Merlin on the Aja cover - Mastodon WPIX channel 11 NY logos Volapük XLIFF "Ones Who Walk Away From Omelas” by Ursula K LeGuin Why Don't We Just Kill the Kid In the Omelas Hole? Taylor Swift - "Change" (2008) - YouTube Taylor Swift - "Mean" (2011) - YouTube Bleachers - "Tiny Moves" - YouTube Kenzo World - YouTubeMargaret Qualley dances her little heart out in this outstanding commercial directed by Spike Jonze. Kenzo World Mirror Shot Breakdown - YouTube @RecDiffs on Mastodon Tokyo DisneySea Review: Simply Incredible - YouTube Sindbad's Storybook Voyage: Tokyo DisneySea's Hidden Gem - YouTube Mystic Manor at Hong Kong Disneyland 2016 - YouTube Maid - Netflix All Too Well: The Short Film - YouTube Go Away Green - Wikipedia"or no-see-um-green" Discover Disney's Color Magic With Go Away Green and Blending Blue! - Inside the Magic Walt Disney World Best Kept Secrets - Magic KingdomListen for the subtle music changes between lands in the MK. Also notice how the pavement changes as well, especially as you travel across the nation and through time from Liberty Square (the Colonial Eastern US) into the Frontierland (western US).  Purkinje effect - WikipediaThe Purkinje effect occurs at the transition between primary use of the photopic (cone-based) and scotopic (rod-based) systems, that is, in the mesopic state: as intensity dims, the rods take over, and before color disappears completel

Notre perception des couleurs varie selon la luminosité. Cette particularité de la vision humaine a été mise en évidence, au XIXe siècle, par l'anatomiste tchèque Jan Evangelista Purkinje, dont les contributions, en matière médicale, sont d'ailleurs des plus variées.Ainsi, ce qu'on appelle l'effet, ou le décalage, Purkinje désigne l'accommodation de notre vision, et spécialement de notre perception des couleurs, à la lumière. Il a ainsi contribué à l'établissement de ce que les spécialistes appellent des "domaines de vision".Chacun d'entre eux correspond à une certaine manière de percevoir les couleurs, en fonction de la quantité de lumière.Un décalage vers le bleuAinsi, la vision "photopique" est celle que l'on expérimente le jour, ou quand les conditions de luminosité sont optimales. Dans une telle situation, ce sont les nuances de rouge qui vont le mieux ressortir.Si l'on regarde un géranium en plein jour, par exemple, ses fleurs, se détachant sur le vert sombre des feuilles, apparaissent en rouge vif.Cependant, l'effet Purkinje opère plutôt dans le cadre de la vision mésopique, quand la lumière du jour commence à baisser, et scotopique, qui désigne la vision nocturne. En effet, dans des conditions de faible éclairage, la vision humaine se décale vers l'autre extrémité du spectre de couleurs, c'est-à-dire vers le bleu.C'est donc en vertu de cet effet Purkinje que, plus la lumière baisse, plus l'on percevra en bleu ces fleurs de géranium qui, en plein soleil, nous semblaient d'un rouge éclatant.Le feuillage de la plante, qui, au grand jour, paraissait plus terne que les fleurs, est perçu comme plus clair quand s'installe une relative obscurité.Cet effet Purkinje peut rendre plus difficile, en astronomie, la mesure de la luminosité de certaines étoiles, dont l'éclat varie à intervalles plus ou moins réguliers.Cette particularité de la vision humaine s'explique par le fonctionnement de l'œil. En effet, cette perception des couleurs tient notamment à la présence des bâtonnets, des cellules responsables de la vision nocturne.Présents dans la rétine, ces bâtonnets contiennent notamment de la rhodopsine, un pigment spécifique qui permet de voir dans la pénombre. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

Notre perception des couleurs varie selon la luminosité. Cette particularité de la vision humaine a été mise en évidence, au XIXe siècle, par l'anatomiste tchèque Jan Evangelista Purkinje, dont les contributions, en matière médicale, sont d'ailleurs des plus variées. Ainsi, ce qu'on appelle l'effet, ou le décalage, Purkinje désigne l'accommodation de notre vision, et spécialement de notre perception des couleurs, à la lumière. Il a ainsi contribué à l'établissement de ce que les spécialistes appellent des "domaines de vision". Chacun d'entre eux correspond à une certaine manière de percevoir les couleurs, en fonction de la quantité de lumière. Un décalage vers le bleu Ainsi, la vision "photopique" est celle que l'on expérimente le jour, ou quand les conditions de luminosité sont optimales. Dans une telle situation, ce sont les nuances de rouge qui vont le mieux ressortir. Si l'on regarde un géranium en plein jour, par exemple, ses fleurs, se détachant sur le vert sombre des feuilles, apparaissent en rouge vif. Cependant, l'effet Purkinje opère plutôt dans le cadre de la vision mésopique, quand la lumière du jour commence à baisser, et scotopique, qui désigne la vision nocturne. En effet, dans des conditions de faible éclairage, la vision humaine se décale vers l'autre extrémité du spectre de couleurs, c'est-à-dire vers le bleu. C'est donc en vertu de cet effet Purkinje que, plus la lumière baisse, plus l'on percevra en bleu ces fleurs de géranium qui, en plein soleil, nous semblaient d'un rouge éclatant. Le feuillage de la plante, qui, au grand jour, paraissait plus terne que les fleurs, est perçu comme plus clair quand s'installe une relative obscurité. Cet effet Purkinje peut rendre plus difficile, en astronomie, la mesure de la luminosité de certaines étoiles, dont l'éclat varie à intervalles plus ou moins réguliers. Cette particularité de la vision humaine s'explique par le fonctionnement de l'œil. En effet, cette perception des couleurs tient notamment à la présence des bâtonnets, des cellules responsables de la vision nocturne. Présents dans la rétine, ces bâtonnets contiennent notamment de la rhodopsine, un pigment spécifique qui permet de voir dans la pénombre. Learn more about your ad choices. Visit megaphone.fm/adchoices

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.552059v1?rss=1 Authors: Christie, J. M., Yang, Z., Zhang, K., Gaffield, M. A., Gross, G. G., Arnold, D. B. Abstract: Climbing fibers supervise cerebellar learning by providing signals to Purkinje cells (PCs) that instruct adaptive changes to mistakenly performed movements. Yet, climbing fibers are regularly active, even during well performed movements, suggesting that a mechanism dynamically regulates the ability of climbing fibers to induce corrective plasticity in response to motor errors. We found that molecular layer interneurons (MLIs), whose inhibition of PCs powerfully opposes climbing-fiber-mediated excitation, serve this function. Optogenetically suppressing the activity of floccular MLIs in mice during the vestibulo-ocular reflex (VOR) induces a learned increase in gain despite the absence of performance errors. Suppressing MLIs when the VOR is mistakenly underperformed reveled that their inhibitory output is necessary to orchestrate gain-increase learning by conditionally permitting climbing fibers to instruct plasticity induction during ipsiversive head turns. Ablation of an MLI circuit for PC disinhibition prevents gain-increase learning during VOR performance errors which was rescued by re-imposing PC disinhibition through MLI activity suppression. Our findings point to a decisive role for MLIs in gating climbing-fiber-mediated learning through their context-dependent inhibition of PCs. 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/2023.07.19.549760v1?rss=1 Authors: Lin, T.-F., Busch, S. E., Hansel, C. Abstract: Non-synaptic ('intrinsic') plasticity of membrane excitability contributes to aspects of memory formation, but it remains unclear whether it merely facilitates synaptic long-term potentiation (LTP), or whether it plays a permissive role in determining the impact of synaptic weight increase. We use tactile stimulation and electrical activation of parallel fibers to probe intrinsic and synaptic contributions to receptive field (RF) plasticity in awake mice during two-photon calcium imaging of cerebellar Purkinje cells. Repetitive activation of both stimuli induced response potentiation that is impaired in mice with selective deficits in either intrinsic plasticity (SK2 KO) or LTP (CaMKII TT305/6VA). Intrinsic, but not synaptic, plasticity expands the local, dendritic RF representation. Simultaneous dendrite and axon initial segment recordings confirm that these dendritic events affect axonal output. Our findings support the hypothesis that intrinsic plasticity provides an amplification mechanism that exerts a permissive control over the impact of LTP on neuronal responsiveness. 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/2023.07.18.549459v1?rss=1 Authors: Gambosi, B., Sheiban, F. J., Biasizzo, M., Antonietti, A., D'Angelo, E. U., Mazzoni, A., Pedrocchi, A. Abstract: Parkinson's disease (PD) is a chronic degenerative disorder of the central nervous system that affects the motor system. The discovery that PD motor symptoms result from the death of dopaminergic cells in the substantia nigra led to focus most of PD research on the basal ganglia. However, recent findings point to an active involvement of the cerebellum in PD. Here, we have developed a multiscale computational model of the rodent brain's basal ganglia-cerebellar network. Simulations showed that a direct effect of dopamine depletion on the cerebellum must be taken into account to reproduce the alterations of PD neural activity, particularly the increased beta oscillations widely reported in PD patients. Moreover, dopamine depletion indirectly impacted spike-time-dependent plasticity at the parallel fiber-Purkinje cell synapses, degrading associative motor learning as observed in PD. Overall, these results suggest a relevant involvement of cerebellum in PD motor symptoms. 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/2023.07.17.549329v1?rss=1 Authors: Moghimyfiroozabad, S., Paul, M. A., Sigoillot, S. M., Selimi, F. Abstract: The C1Q complement protein C1QL1 is highly conserved in mammals where it is expressed in various tissues including the brain. This secreted protein interacts with Brain-specific Angiogenesis Inhibitor 3, BAI3/ADGRB3, and controls synapse formation and maintenance. C1ql1 is expressed in the inferior olivary neurons that send projections to cerebellar Purkinje cells, but its expression in the rest of the brain is less documented. To map C1ql1 expression and enable the specific targeting of C1ql1-expressing cells, we characterized a knockin mouse model expressing the Cre recombinase under the control of C1ql1 regulatory sequences. We characterized the capacity for Cre-driven recombination in the brain and mapped Cre expression in various neuron types using reporter mouse lines. Using an intersectional strategy with viral particle injections, we show that this mouse line can be used to target specific afferents of Purkinje cells. As C1ql1 is also expressed in other regions of the brain, as well as in other tissues such as adrenal glands, placenta, colon and testis, our mouse model is a useful tool to target C1ql1-expressing cells in a broad variety of tissues. 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/2023.07.12.548720v1?rss=1 Authors: Nashef, A., Spindle, M. S., Calame, D. J., Person, A. L. Abstract: Cerebellar Purkinje cells (PCs) encode movement kinematics in their population firing rates. Firing rate suppression is hypothesized to disinhibit neurons in the cerebellar nuclei, promoting adaptive movement adjustments. Debates persist, however, about whether a second disinhibitory mechanism, PC simple spike synchrony, is a relevant population code. We addressed this question by relating PC rate and synchrony patterns recorded with high density probes, to mouse reach kinematics. We discovered behavioral correlates of PC synchrony that align with a known causal relationship between activity in cerebellar output. Reach deceleration was positively correlated with both Purkinje firing rate decreases and synchrony, consistent with both mechanisms disinhibiting target neurons, which are known to adjust reach velocity. Direct tests of the contribution of each coding scheme to nuclear firing using dynamic clamp, combining physiological rate and synchrony patterns ex vivo, confirmed that physiological levels of PC simple spike synchrony are highly facilitatory for nuclear firing. These findings suggest that PC firing rate and synchrony collaborate to exert fine control of movement. 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/2023.07.03.547586v1?rss=1 Authors: Salazar Leon, L. E., Brown, A. M., Kaku, H., Sillitoe, R. V. Abstract: Purkinje cell dysfunction causes movement disorders such as ataxia, however, recent evidence suggests that Purkinje cell dysfunction may also alter sleep regulation. Here, we used an ataxia mouse model generated by silencing Purkinje cell neurotransmission (L7Cre;Vgatfx/fx) to better understand how cerebellar dysfunction impacts sleep physiology. We focused our analysis on sleep architecture and electrocorticography (ECoG) patterns based on their relevance to extracting physiological measurements during sleep. We found that circadian activity is unaltered in the mutant mice, although their sleep parameters and ECoG patterns are modified. The L7Cre;Vgatfx/fx mutant mice have decreased wakefulness and rapid eye movement (REM) sleep, while non-rapid eye movement (NREM) sleep is increased. The mutant mice have an extended latency to REM sleep, which is also observed in human ataxia patients. Spectral analysis of ECoG signals revealed alterations in the power distribution across different frequency bands defining sleep. Therefore, Purkinje cell dysfunction may influence wakefulness and equilibrium of distinct sleep stages in ataxia. Our findings posit a connection between cerebellar dysfunction and disrupted sleep and underscore the importance of examining cerebellar circuit function in sleep disorders. 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/2023.06.22.546199v1?rss=1 Authors: Soetedjo, R., Horwitz, G. Abstract: Internal models are essential for the production of accurate movements. The accuracy of saccadic eye movements is thought to be mediated by an internal model of orbital mechanics encoded in the cerebellum. The cerebellum may also be part of a feedback loop that predicts the displacement of the eye in real time and compares the predicted displacement to the desired displacement command to ensure that saccades land on target. To investigate the role of the cerebellum in these two aspects of saccade production, we delivered saccade-triggered light pulses to channelrhodopsin-2-expressing Purkinje cells in the oculomotor vermis (OMV) of two macaque monkeys. Light pulses delivered during the acceleration phase slowed the deceleration phase of ipsiversive saccades. The long latency of these effects, and their scaling with light pulse duration, are consistent with an integration of neural signals downstream of the stimulation. In contrast, light pulses delivered during contraversive saccades reduced saccade velocity at a short latency (~6 ms) that was followed by a compensatory reacceleration which caused gaze to land near or on the target. We conclude that the contribution of the OMV to saccade control depends on saccade direction; the ipsilateral OMV is part of a forward model that predicts eye displacement, whereas the contralateral OMV is part of an inverse model that creates the force required to move the eyes accurately. 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/2023.06.26.546542v1?rss=1 Authors: Cook, A. A., Leung, T. C. S., Rice, M., Nachman, M., Zadigue-Dube, E., Watt, A. J. Abstract: Spinocerebellar ataxia type 6 (SCA6) is a rare disease that is characterized by cerebellar dysfunction. Patients have progressive motor coordination impairment, and postmortem brain tissue reveals degeneration of cerebellar Purkinje cells and a reduced level of cerebellar brain-derived neurotrophic factor (BDNF). However, the pathophysiological changes underlying SCA6 are not fully understood. We carried out RNA sequencing of cerebellar vermis tissue in a mouse model of SCA6, which revealed widespread dysregulation of genes associated with the endo-lysosomal system. Since disruption to endosomes or lysosomes could contribute to cellular deficits, we examined the endo-lysosomal system in SCA6. We identified alterations in multiple endosomal compartments in the Purkinje cells of SCA6 mice. Early endosomes were enlarged, while the size of the late endosome compartment was reduced. We also found evidence for impaired trafficking of cargo to the lysosomes. As the proper functioning of the endo-lysosomal system is crucial for the sorting and trafficking of signaling molecules, we wondered whether these changes could contribute to previously identified deficits in signaling by BDNF and its receptor tropomyosin kinase B (TrkB) in SCA6. Indeed, we found that the enlarged early endosomes in SCA6 mice accumulated both BDNF and TrkB. Furthermore, TrkB recycling to the cell membrane in recycling endosomes was reduced, and the late endosome transport of BDNF for degradation was impaired. Therefore, mis-trafficking due to aberrant endo-lysosomal transport and function could contribute to SCA6 pathophysiology through alterations to BDNF-TrkB signaling, as well as mishandling of other signaling molecules. Deficits in early endosomes and BDNF localization were rescued by chronic administration of a TrkB agonist, 7,8-DHF, that we have previously shown restores motor coordination and cerebellar TrkB expression. The endo-lysosomal system is thus both a novel locus of pathophysiology in SCA6, and a promising therapeutic target. 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/2023.04.24.538082v1?rss=1 Authors: Mätlik, K., Baffuto, M., Kus, L., Davis, D. A., Paul, M. R., Carroll, T. S., Heintz, N. Abstract: Tissue-specific somatic expansion of the mutant Huntingtin (mHTT) CAG tract and regional degeneration of the brain are key features of Huntington's disease (HD). However, the relationships between somatic CAG expansion, death of specific cell types, and molecular events associated with these processes have not been established. Here we employed fluorescence-activated nuclear sorting (FANS) and deep molecular profiling to gain insight into the properties of cell types of the human striatum and cerebellum in HD and control donors. Expansion of the mHTT CAG tract occurs in striatal MSNs and cholinergic interneurons, in cerebellar Purkinje cells, and at the mutant ATXN3 locus in MSN nuclei from SCA3 donors. Somatic CAG tract instability in MSNs is associated with higher levels of MSH2 and MSH3. Our data indicate that somatic CAG tract expansion is not sufficient for cell death, and identify transcriptional changes associated with somatic CAG expansion and toxicity in the human striatum. 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/2023.04.16.537034v1?rss=1 Authors: Muller, S. Z., Pi, J. S., Hage, P., Fakharian, M. A., Sedaghat-Nejad, E., Shadmehr, R. Abstract: The cerebellar cortex performs computations that are critical for control of our actions, and then transmits that information via simple spikes of Purkinje cells (P-cells) to downstream structures. However, because P-cells are many synapses away from muscles, we do not know how their output affects behavior. Furthermore, we do not know the level of abstraction, i.e., the coordinate system of the P-cell's output. Here, we recorded spiking activities of hundreds of P-cells in the oculomotor vermis of marmosets during saccadic eye movements and found that following the presentation of a visual stimulus, the olivary input to a P-cell encoded a probabilistic signal that coarsely described both the direction and the amplitude of that stimulus. When this input was present, the resulting complex spike briefly suppressed the P-cell's simple spikes, disrupting the P-cell's output during that saccade. Remarkably, this brief suppression altered the saccade's trajectory by pulling the eyes toward the part of the visual space that was preferentially encoded by the olivary input to that P-cell. Thus, analysis of behavior in the milliseconds following a complex spike unmasked how the P-cell's output influenced behavior: the preferred location in the coordinates of the visual system as conveyed probabilistically from the inferior olive to a P-cell defined the action in the coordinates of the motor system for which that P-cell's simple spikes directed behavior. 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/2023.04.13.536796v1?rss=1 Authors: Lin, L. L., Torres, M., Pederson, B., Wang, H. H., Wei, X., Li, Z. J., Liu, X., Mao, H., Hanzel, M., Govek, E. E., Lu, Y., Wang, H., Zhao, Z., Hatten, M. E., Sun, S. E., Qi, L. Abstract: Despite recent advances in our understanding of the physiological importance of SEL1L-HRD1 endoplasmic reticulum (ER)-associated protein degradation (ERAD) using cell type-specific knockout (KO) mouse models, its relevance and importance in ataxia pathogenesis remain unknown. Here we show that loss of SEL1L-HRD1 ERAD complex interaction or function in Purkinje cells leads to cerebellar ataxia. Both homozygous knock-in (KI) mice carrying SEL1L variant p.Ser658Pro (S658P) and mice with Purkinje cell-specific deletion of SEL1L exhibit early-onset cerebellar ataxia, although disease severity and progression differ between the models. Structure-function analyses reveal that SEL1L S658P variant impairs, not abolishes, ERAD function by attenuating the interaction between SEL1L and HRD1. Proteomic screen of potential endogenous substrates leads to the identification of Astrotactin 1 and 2, two integral membrane proteins involved in neuronal function and development, whose maturation and biogenesis in the ER depend on SEL1L-HRD1 ERAD activity. These data demonstrate the pathophysiological importance of SEL1L-HRD1 interaction and function in the pathogenesis of cerebellar ataxia. 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/2023.04.11.535633v1?rss=1 Authors: Yan, Y., Murphy, T. H. Abstract: The cerebellum participates in motor tasks, but also a broad spectrum of cognitive functions. However, cerebellar connections with higher areas such as cortex are not direct and the mechanisms by which the cerebellum integrates and processes diverse information streams are not clear. We investigated the functional connectivity between single cerebellar neurons and population activity of the dorsal cortex using mesoscale imaging. Our findings revealed dynamic coupling between individual cerebellar neurons and diverse cortical networks, and such functional association can be influenced by local excitatory and inhibitory connections. While the cortical representations of individual cerebellar neurons displayed marked changes across different brain states, the overall assignments to specific cortical topographic areas at the population level remained stable. Simple spikes and complex spikes of the same Purkinje cells displayed either similar or distinct cortical functional connectivity patterns. Moreover, the spontaneous functional connectivity patterns aligned with cerebellar neurons' functional responses to external stimuli in a modality-specific manner. Importantly, the tuning properties of subsets of cerebellar neurons differed between anesthesia and awake states, mirrored by state-dependent changes in their long-range functional connectivity patterns. Collectively, our results provide a comprehensive view of the state-dependent cortical-cerebellar functional connectivity landscape and demonstrate that remapping of long-range functional network association could underlie state-dependent change in sensory processing. 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/2023.03.30.534913v1?rss=1 Authors: Leister, H., Krause, F. F., Gil, B., Prus, R., Prus, I., Hellhund-Zingel, A., Mitra, M., Da Rosa Gerbatin, R., Delanty, N., Beausang, A., Brett, F. M., Farrell, M. A., Cryen, J., O'Brien, D. F., Henshall, D., Helmprobst, F., Pagenstecher, A., Steinhoff, U., Visekruna, A., Engel, T. Abstract: The immunoproteasome is a central protease complex required for optimal antigen presentation. Immunoproteasome activity is also associated with facilitating degradation of misfolded and oxidized proteins, which prevents cellular stress. While extensively studied during diseases with increasing evidence suggesting a role for the immunoproteasome during pathological conditions including neurodegenerative diseases, this enzyme complex is believed to be mainly inactive in the healthy brain. Here, we show an age-dependent increase in polyubiquitination in the brain of wild-type mice, accompanied with induction of immunoproteasomes, which was most prominent in neurons and microglia. In contrast, mice completely lacking immunoproteasomes (triple-knockout (TKO) mice deficient for LMP2, LMP7 and MECL-1), displayed a strong increase in polyubiquitinated proteins already in the young brain and developed spontaneous epileptic seizures, beginning at the age of 6 months. Injections of kainic acid led to high epilepsy-related mortality of aged TKO mice, confirming increased pathological hyperexcitability states. Notably, the expression of the immunoproteasome was reduced in the brains of patients suffering from epilepsy. In addition, aged TKO mice showed increased anxiety, tau hyperphosphorylation and degeneration of Purkinje cell population with the resulting ataxic symptoms and locomotion alterations. Collectively, our study suggests a critical role for the immunoproteasome in the maintenance of a healthy brain during aging. 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/2023.03.27.534425v1?rss=1 Authors: Busch, S. E., Hansel, C. Abstract: In rodents, most Purkinje cells in the adult cerebellum receive one climbing fiber from the inferior olive. In postnatal competition for innervation of the growing primary dendrite, one "winner" climbing fiber prevails, while surplus fibers are eliminated. It is unknown if the presence of multiple primary dendrites - which we describe as nearly universal in human - might allow multiple climbing fibers to survive. Mouse cerebellum provides a useful model for investigation as a minority of Purkinje cells exhibit polydendritic architecture. Among mature cells with multiple primary dendrites, ~25% are indeed innervated by multiple climbing fibers. Two-photon calcium imaging in vivo demonstrates that separate primary dendrites can have distinct response properties to sensory stimulation, suggesting that polydendritic Purkinje cells integrate functionally independent climbing fiber receptive fields. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

¿Te has dado cuenta de que, en situaciones en las que nos movemos en el día a día, con poca luz, se suelen usar luces rojas? Te explico el por qué: Purkinje tiene la culpa. Espero tus comentarios en la comunidad de Telegram: https://t.me/cienciaoficcion

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.17.533173v1?rss=1 Authors: Gruver, K. M., Y, J. W., Fields, E., Song, S., Sjostrom, P. J., Watt, A. J. Abstract: Circuits in the brain are built from connections between neurons, where the spatial organization and functional properties of these connections determines circuit function. In the cerebellum, Purkinje cells transmit information to neurons in the cerebellar nuclei, but how Purkinje cell - nuclear neuron connections are organized remains unclear. Here, we explored the connections between Purkinje cells and cerebellar nuclear neurons using whole-cell electrophysiology and optogenetics to produce spatial connectivity maps of cerebellar cortical output. We observed non-random connectivity between Purkinje cells and their target neurons, with inputs to cerebellar nuclear neurons clustering along cerebellar transverse zones. While many nuclear neurons received inputs from a single zone, a number of different connectivity motifs were observed. Neurons receiving inputs from all four zones were more common than predicted by a random model and showed topographic organization in the nucleus. Finally, we observed that small Purkinje cell inputs were sufficient to pause the output of nuclear neurons, suggesting that widespread Purkinje cell synchrony may not be necessary to influence cerebellar output. These findings reveal cerebellar nuclear neurons as an important locus of multimodal cerebellar integration. 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/2023.03.08.531672v1?rss=1 Authors: Masoli, S., Sanchez-Ponce, D., Vrieler, N., Abu-Haya, K., Lerner, V., Shahar, T., Nedelescu, H., Rizza, M. F., Benavides-Piccione, R., DeFelipe, J., Yarom, Y., Munoz, A., D'Angelo, E. Abstract: Purkinje cells (PC) of the cerebellum are amongst the largest neurons of the brain and have been extensively investigated in rodents. However, their morphological and physiological properties in humans are still poorly understood. Here, we have taken advantage of high-resolution morphological reconstructions and of unique electrophysiological recordings of human PCs ex vivo to generate computational models and estimate computational capacity. An inter-species comparison showed that human PCs had similar fractal structure but were bigger than mouse PCs. Consequently, given a similar spine density (2/micrometer), human PCs hosted about 5 times more dendritic spines. Moreover, human had higher dendritic complexity than mouse PCs and usually emitted 2-3 main dendritic trunks instead than 1. Intrinsic electroresponsiveness was similar in the two species but model simulations revealed that the dendrites generated ~6.5 times (n=51 vs. n=8) more combinations of independent input patterns in human than mouse PCs leading to an exponential 2n increase in Shannon information. Thus, while during evolution human PCs maintained similar patterns of spike discharge as in rodents, they developed more complex dendrites enhancing computational capacity up to the limit of 10 billion times. 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/2023.03.06.531306v1?rss=1 Authors: Conti, R., Auger, C. Abstract: Granule cells of the cerebellum make up to 175 000 excitatory synapses on a single Purkinje cell, encoding information from the mossy fibre inputs into the cerebellar cortex. The granule cell axon is made of an ascending portion and a long parallel fibre formed at right angle. There are controversial indications that ascending axon (AA) and parallel fibre (PF) synapse properties and modalities of plasticity are different. We tested the hypothesis that if AA and PF synapses are different, and encode different information, association of the inputs to Purkinje cells might be relevant to the circuit and might trigger plasticity, as does the coincident timing of parallel fibre and climbing fibre inputs. Here we describe a new form of associative plasticity between granule cell inputs. We show for the first time that AA and PF synchronous and repetitive train stimulation, with inhibition intact, triggers long term potentiation (LTP) at AA synapses and long term depression (LTD) at PF synapses. AA-LTP is associative and relies on the costimulation with PFs. AA-LTP is time dependent and the timing of presentation of the two inputs controls the outcome of plasticity. Finally, we show that both NMDAR and mGluR activation is required to induce AA-LTP. These observations reinforce the suggestion that AA and PF synapses are two synaptic populations with different coding capabilities and plasticity, governed by different modalities. Associative plasticity of AA and PF synapses enables effective association of different information, although both are transmitted via granule cells. 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/2023.02.20.529180v1?rss=1 Authors: Janeckova, L., Knotek, T., Kriska, J., Hermanova, Z., Kirdajova, D., Kubovciak, J., Berkova, L., Tureckova, J., Camacho Garcia, S., Galuskova, K., Kolar, M., Anderova, M., Korinek, V. Abstract: Glia cells expressing neuron-glial antigen 2 (NG2) play a critical role as oligodendrocyte precursor cells (OPCs) in the healthy brain; however, their differentiation potential after ischemic injury remains an unresolved question. Here, we aimed to elucidate the heterogeneity and role of NG2 glia in the ischemic brain. We used transgenic mice to label NG2-expressing cells and their progeny with red fluorescent protein tdTomato in the healthy brains and those after focal cerebral ischemia (FCI). Based on single-cell RNA sequencing, the labeled glial cells were divided into five distinct subpopulations. The identity of these subpopulations was determined based on gene expression patterns. In addition, membrane properties were further analyzed using the patch-clamp technique. Three of the observed subpopulations represented OPCs, whereas the fourth group exhibited characteristics of cells destined for oligodendrocyte fate. The fifth subpopulation of NG2 glia carried astrocytic markers. Importantly, we detected features of neural progenitors in these cells. This subpopulation was present in both healthy and post-ischemic tissue; however, its gene expression changed after ischemia, with genes related to neurogenesis being more abundant. Neurogenic gene expression was monitored over time and complemented by immunohistochemical staining, which showed increased numbers of Purkinje cell protein 4-positive NG2 cells at the edge of the ischemic lesion 12 days after FCI, and NeuN-positive NG2 cells 28 days after injury, indicating the existence of neuron-like cells that develop from NG2 glia in the ischemic tissue. Our results provide further insight into the differentiation plasticity and neurogenic potential of NG2 glia after stroke. 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/2023.02.18.529047v1?rss=1 Authors: Sanchez-Leon, C. A., Sanchez-Garrido Campos, G., Fernandez, M., Sanchez-Lopez, A., Medina, J. F., Marquez-Ruiz, J. Abstract: Transcranial direct-current stimulation (tDCS) is a promising non-invasive neuromodulatory technique being proposed for treating neurologic disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo. In this study, we observe a heterogeneous polarity modulation of the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex. Using a combination of juxtacellular labeling and high-density Neuropixels recordings, we demonstrate that the apparently heterogeneous effects of tDCS on PC activity can be fully explained by taking into account the somatodendritic orientation relative to the electric field. Our findings emphasize the importance of considering neuronal orientation and morphological aspects to increase the predictive power of tDCS computational models and optimize desired effects in basic and clinical human applications. 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/2023.02.17.529019v1?rss=1 Authors: Herzfeld, D. J., Joshua, M., Lisberger, S. G. Abstract: Control of movement requires the coordination of multiple brain areas, each containing populations of neurons that receive inputs, process these inputs via recurrent dynamics, and then relay the processed information to downstream populations. Information transmission between neural populations could occur through either coordinated changes in firing rates or the precise transmission of spike timing. We investigate the nature of the code for transmission of signals to downstream areas from a part of the cerebellar cortex that is crucial for the accurate execution of a quantifiable motor behavior. Simultaneous recordings from Purkinje cell pairs in the cerebellar flocculus of rhesus macaques revealed how these cells coordinate their activity to drive smooth pursuit eye movements. Purkinje cells show millisecond-scale coordination of spikes (synchrony), but the level of synchrony is small and likely insufficient to impact the firing of downstream neurons in the vestibular nucleus. Further, analysis of previous metrics for assaying Purkinje cell synchrony demonstrates that these metrics conflate changes in firing rate and neuron-neuron covariance. We conclude that the output of the cerebellar cortex uses primarily a rate code rather than synchrony code to drive activity of downstream neurons and thus control motor behavior. 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/2023.02.09.527916v1?rss=1 Authors: Leon, L. E. S., Sillitoe, R. V. Abstract: Although dystonia is the third most common movement disorder, patients often also experience debilitating nonmotor defects including impaired sleep. The cerebellum is a central component of a ''dystonia network'' that plays various roles in sleep regulation. Importantly, the primary driver of sleep impairments in dystonia remains poorly understood. The cerebellum, along with other nodes in the motor circuit, could disrupt sleep. However, it is unclear how the cerebellum might alter sleep and mobility. To disentangle the impact of cerebellar dysfunction on motion and sleep, we generated two mouse genetic models of dystonia that have overlapping cerebellar circuit miswiring but show differing motor phenotype severity: Ptf1aCre;Vglut2fx/fx and Pdx1Cre;Vglut2fx/fxmice. In both models, excitatory climbing fiber to Purkinje cell neurotransmission is blocked, but only the Ptf1aCre;Vglut2fx/fx mice have severe twisting. Using in vivo ECoG and EMG recordings we found that both mutants spend greater time awake and in NREM sleep at the expense of REM sleep. The increase in awake time is driven by longer awake bouts rather than an increase in bout number. We also found a longer latency to reach REM in both mutants, which is similar to what is reported in human dystonia. We uncovered independent but parallel roles for cerebellar circuit dysfunction and motor defects in promoting sleep quality versus posture impairments in dystonia. 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/2023.01.31.526333v1?rss=1 Authors: Munoz-Estrada, J., Nguyen, A. V., Goetz, S. C. Abstract: Frameshift mutations in Tau Tubulin Kinase 2 (TTBK2) cause spinocerebellar ataxia type 11 (SCA11), which is characterized by the progressive loss of Purkinje cells and cerebellar atrophy. Previous work showed that these TTBK2 variants generate truncated proteins that interfere with primary ciliary trafficking and with Sonic Hedgehog (SHH) signaling in mice. Nevertheless, the molecular mechanisms underlying the dominant interference of mutations remain unknown. Herein, we discover that SCA11-associated variants contain a bona fide peroxisomal targeting signal type 1. We find that their expression in RPE1 cells reduces peroxisome numbers within the cell and at the base of the cilia, disrupts peroxisome fission pathways, and impairs trafficking of ciliary SMO upon SHH signaling activation. This work uncovers a neomorphic function of SCA11-causing mutations and identifies requirements for both peroxisomes and cholesterol in trafficking of cilia-localized SHH signaling proteins. In addition, we postulate that molecular mechanisms underlying cellular dysfunction in SCA11 converge on the SHH signaling pathway. 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/2023.01.03.521946v1?rss=1 Authors: Paul, M. A., Sigoillot, S. M., Marti, L., Delagrange, M., Mailly, P., Selimi, F. Abstract: Brain function relies on the generation of a large variety of morphologically and functionally diverse, but specific, neuronal synapses. Here, we show that, initially, synapse formation on a common target neuron, the cerebellar Purkinje cells, involves a presynaptic secreted protein common for all types of excitatory inputs. The molecular program then evolves only in one of the inputs with the additional expression of a combination of presynaptic secreted proteins that specify the mature pattern of connectivity on the target. These results show that some inputs actively and gradually specify their synaptic molecular identity while others rely on the "original code". Thus, the molecular specification of excitatory synapses, crucial for proper circuit function, is acquired in a stepwise manner during mouse postnatal development and obeys input-specific 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/2022.12.06.519418v1?rss=1 Authors: Iwane, F., Iturrate, I., Chavarriaga, R., Millan, J. d. R. Abstract: Error-related potentials (ErrP) are a prominent electroencephalogram (EEG) correlate of performance monitoring, and so crucial for learning and adapting our behavior. Although there exists an agreement that ErrP signal awareness to errors, it remains poorly understood whether they encode further information. Here we report an experiment with sixteen participants during three recording sessions in which occasional visuomotor rotations of varying magnitude occurred during a cursor reaching task. We designed a brain-computer interface (BCI) to detect ErrP in single trials that provided real-time feedback to participants by changing the color of the cursor upon ErrP detection. The individual ErrP-BCI decoders exhibited good transfer across recording sessions and scalability over the varying magnitude of errors. Our results indicate that ErrPs encode not only the conscious perception of errors, but also their magnitude, in their amplitude and latency. Furthermore, a non-linear relationship between the ErrP-BCI output and the magnitude of errors predicts individual perceptual thresholds to detect rotations. The uncovered relationship is consistent with non-human primate studies, which found a similar relationship between the size of errors and simple spike activity of Purkinje cells, and we conjecture a cerebellar contribution to ErrP. Our experimental setup and findings open new avenues to probe and extend current theories of performance monitoring, which are based on response conflict tasks, by incorporating continuous human-interaction tasks as well as analysis of the ErrP complex as a whole rather than individual peaks. 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/2022.12.05.518634v1?rss=1 Authors: Hoang, H., Tsutsumi, S., Matsuzaki, M., Kano, M., Kawato, M., Kitamura, K., Toyama, K. Abstract: Dynamic functional organization by synchronization is theorized to be essential for dimension reduction of the cerebellar learning space. We analyzed a large amount of coordinate-localized, two-photon imaging data from cerebellar Crus II in mice undergoing Go/No-go reinforcement learning. Tensor component analysis revealed that a majority of climbing fiber inputs to Purkinje cells were reduced to only four functional components, corresponding to accurate timing control of motor initiation related to a Go cue, cognitive error-based learning, reward processing, and inhibition of erroneous behaviors after a No-go cue. Spatial distribution of these components coincided well with the boundaries of Aldolase-C/zebrin II expression in Purkinje cells, whereas several components are mixed in single neurons. Synchronization within individual components was bidirectionally regulated according to specific task contexts and learning stages. These findings suggest that the cerebellum, based on anatomical compartments, reduces dimensions by self-organization of components, a feature that may inspire new-generation AI designs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The signaling molecule's social role in the ‘little brain' involves Purkinje neurons in the Crus I and Crus II regions, a new study reveals. The post Mouse study links dopamine in cerebellum to social behavior appeared first on Spectrum | Autism Research News.

The signaling molecule's social role in the ‘little brain' involves Purkinje neurons in the Crus I and Crus II regions, a new study reveals.

The signaling molecule's social role in the ‘little brain' involves Purkinje neurons in the Crus I and Crus II regions, a new study reveals.

Discussion of how our perception of blues and greens remain strong in low light, and how that may have impacted the use of lapis lazuli (and other blue pigments) prior to the invention of the electric light bulb.

This week is "electric"! Would your heart really continue beating if it were suddenly torn from your body? What is a cardiac arrhythmia? And why on earth are there so many abbreviations used in cardiology? With the exception of the last one, the answers can be found this week as we explore the conduction system of the heart. Terms we discuss are; The Sinoatrial (SA) node, Atrioventricular (AV) node, Bundle of His, left and right bundle branches, and the Purkinje fibres. Now you see why we abbreviate..... catchy!

Interviewed Ben Davis, of seminal Atlanta math rock band The Purkinje Shift. This is the first 'episode' of a podcast I'm calling Loving the Void. More to come. Please check out these links to learn more: thepurkinjeshift.bandcamp.com/ chunklet.bandcamp.com/album/threads beyondfailure.blogspot.com/2010/07/pur…-shift.html roomsalon.bandcamp.com/releases --- Support this podcast: https://podcasters.spotify.com/pod/show/jamiel-alkhaja/support