PaperPlayer biorxiv neuroscience

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551761v1?rss=1 Authors: Methi, A., Islam, M. R., Kaurani, L., Sakib, M. S., Krueger, D. M., Burkhardt, S., Liebetanz, D., Fischer, A. Abstract: Exercise has been recognized as a beneficial factor for cognitive health, particularly in relation to the hippocampus, a vital brain region responsible for learning and memory. Previous research has demonstrated that exercise-mediated improvement of learning and memory in humans and rodents correlates with increased adult neurogenesis and processes related to enhanced synaptic plasticity. Nevertheless, the underlying molecular mechanisms are not fully understood. With the aim to further elucidate these mechanisms we provide a comprehensive dataset of the mouse hippocampal transcriptome at the single-cell level after four weeks of voluntary wheel-running. Our analysis provides a number of interesting observations. For example, the results suggest that exercise affects adult neurogenesis by accelerating the maturation of a subpopulation of Prdm16-expressing neurons. Moreover, we uncover the existence of an intricate crosstalk among multiple vital signaling pathways such as NF-{kappa}B, Wnt/{beta}-catenin, Notch, retinoic acid (RA) pathways altered upon exercise in a specific cluster of excitatory neurons within the Cornu Ammonis (CA) region of the hippocampus. In conclusion, our study provides an important resource dataset and sheds further light on the molecular changes induced by exercise in the hippocampus. These findings have implications for developing targeted interventions aimed at optimizing cognitive health and preventing age-related cognitive decline. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551724v1?rss=1 Authors: Harris, T. D., Yuan, A. X., Colonell, J. I., Lebedeva, A., Charles, A. Abstract: Accurate tracking of the same neurons across multiple days is crucial for studying changes in neuronal activity during learning and adaptation. New advances in high density extracellular electrophysiology recording probes, such as Neuropixels, provide a promising avenue to accomplish this goal. Identifying the same neurons in multiple recordings is, however, complicated by non-rigid movement of the tissue relative to the recording sites (drift) and loss of signal from some neurons. Here we propose a neuron tracking method that can identify the same cells independent of firing statistics, which are used by most existing methods. Our method is based on between-day non-rigid alignment of spike sorted clusters. We verified the same cell identify using measured visual receptive fields. This method succeeds on datasets separated from one to 47 days, with an 86% average recovery rate. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551743v1?rss=1 Authors: Adeli, H., Minni, S., Kriegeskorte, N. Abstract: The Algonauts challenge (Gifford et al. [2023]) called on the community to provide novel solutions for predicting brain activity of humans viewing natural scenes. This report provides an overview and technical details of our submitted solution. We use a general transformer encoder-decoder model to map images to fMRI responses. The encoder model is a vision transformer trained using self-supervised methods (DINOv2). The decoder uses queries corresponding to different brain regions of interests (ROI) in different hemispheres to gather relevant information from the encoder output for predicting neural activity in each ROI. The output tokens from the decoder are then linearly mapped to the fMRI activity. The predictive success (challenge score: 63.5229, rank 2) suggests that features from self-supervised transformers may deserve consideration as models of human visual brain representations and shows the effectiveness of transformer mechanisms (self and cross-attention) to learn the mapping from features to brain responses. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551732v1?rss=1 Authors: Gaynes, J. A., Budoff, S. A., Grybko, M. J., Poleg-Polsky, A. Abstract: The processing of visual information by retinal starburst amacrine cells (SACs) involves transforming excitatory input from bipolar cells (BCs) into directional calcium output. While previous studies have suggested that an asymmetry in the kinetic properties of bipolar cells along the soma-dendritic axes of the postsynaptic cell could enhance directional tuning at the level of individual branches, it remains unclear whether biologically relevant presynaptic kinetics contribute to direction selectivity when visual stimulation engages the entire dendritic tree. To address this question, we built multicompartmental models of the bipolar-SAC circuit and trained them to boost directional tuning. We report that despite significant dendritic crosstalk and dissimilar directional preferences along the dendrites that occur during whole-cell stimulation, the rules that guide BC kinetics leading to optimal directional selectivity are similar to the single-dendrite condition. To correlate model predictions to empirical findings, we utilized two-photon glutamate imaging to study the dynamics of bipolar release onto ON- and OFF-starburst dendrites in the murine retina. We reveal diverse presynaptic dynamics in response to motion in both BC populations; algorithms trained on the experimental data suggested that the differences in the temporal release kinetics are likely to correspond to heterogeneous receptive field (RF) properties among the different BC types, including the spatial extent of the center and surround components. In addition, we demonstrate that circuit architecture composed of presynaptic units with experimentally recorded dynamics could enhance directional drive but not to levels that replicate empirical findings, suggesting other DS mechanisms are required to explain SAC function. Our study provides new insights into the complex mechanisms underlying direction selectivity in retinal processing and highlights the potential contribution of presynaptic kinetics to the computation of visual information by starburst amacrine 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/2023.08.02.551674v1?rss=1 Authors: Omondi, C., Chou, A., Fond, K. A., Morioka, K., Joseph, N. R., Sacramento, J. A., Lorio, E., Torres-Espin, A., Radabaugh, H. L., Davis, J. A., Gumbel, J. H., Huie, J. R., Ferguson, A. R. Abstract: Western blot is a popular biomolecular analysis method for measuring the relative quantities of independent proteins in complex biological samples. However, variability in quantitative western blot data analysis poses a challenge in designing reproducible experiments. The lack of rigorous quantitative approaches in current western blot statistical methodology may result in irreproducible inferences. Here we describe best practices for the design and analysis of western blot experiments, with examples and demonstrations of how different analytical approaches can lead to widely varying outcomes. To facilitate best practices, we have developed the blotRig tool for designing and analyzing western blot experiments to improve their rigor and reproducibility. The blotRig application includes functions for counterbalancing experimental design by lane position, batch management across gels, and analytics with covariates and random effects. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551722v1?rss=1 Authors: Tunca, M. B., Rezaki, A., Nizamoglu, H., Urgen, B. A. Abstract: Perceptual load theory argues that attention is a limited resource and stimuli cannot be processed if there is insufficient perceptual capacity available. Although attention is known to modulate biological motion processing, whether this modulation differs among different perceptual loads remains unknown. To answer this question, three experiments are conducted in which biological motion is utilized as a task-irrelevant distractor. The first experiment showed that biological motion is processed differently than non-biological motion across different perceptual load conditions. The second experiment investigated the effect of attention on biological motion processing, revealing that higher eccentricities enhance biological motion processing but only when the perceptual load is low. The last experiment investigated the same question but with cortically magnified stimuli. It found that when the stimuli are cortically magnified, the enhancement effect of eccentricity is present regardless of the perceptual load. Overall, the results suggest that perceptual load modulates the processing of task-irrelevant biological motion and interacts with other factors (such as eccentricity) that modulate this 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/2023.08.02.551706v1?rss=1 Authors: Perez, C. I., Luis-Islas, J., Lopez, A., Diaz, X., Molina, O., Arroyo, B., Moreno, M. G., Lievana, E. G., Fonseca, E., Castaneda-Hernandez, G., Gutierrez, R. Abstract: Obesity is a major global health epidemic that has adverse effects on both the people affected as well as the cost to society. Several anti-obesity drugs that target GLP-1 receptors have recently come to the market. Here we describe the effects of tesofensine, a novel anti-obesity drug that acts as a triple monoamine neurotransmitter reuptake inhibitor. We investigated its effects on weight loss and underlying neuronal mechanisms in mice and rats using various techniques. These include behavioral tasks, DeepLabCut videotaped analysis, electrophysiological ensemble recordings, optogenetic activation, and chemogenetic silencing of GABAergic neurons in the Lateral Hypothalamus (LH). We found that tesofensine induced greater weight loss in obese than lean rats, which was associated with changes in LH ensemble activity. In Vgat-ChR2 and Vgat-IRES-cre transgenic mice, we found for the first time that tesofensine inhibited a subset of LH GABAergic neurons, reducing their ability to promote feeding behavior, and chemogenetically silencing them enhanced tesofensine's food-suppressing effects. Unlike phentermine, a dopaminergic appetite suppressant, tesofensine causes few, if any, head-weaving stereotypy at therapeutic doses. Most importantly, we found that tesofensine prolonged the weight loss induced by 5-HTP, a serotonin precursor, and blocked the body weight rebound that often occurs after weight loss. Behavioral studies on rats with the tastant sucrose indicated that tesofensine's appetite suppressant effects are independent of taste aversion and do not directly affect the perception of sweetness or palatability of sucrose. In summary, our data provide new insights into the effects of tesofensine on weight loss and the underlying neuronal mechanisms, suggesting that tesofensine may be an effective treatment for obesity and that it may be a valuable adjunct to other appetite suppressants to prevent body weight rebound. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551576v1?rss=1 Authors: Kashyap, S., Oliveira, I. A. F., Uludag, K. Abstract: Cerebral blood flow (CBF) is a critical physiological parameter of brain health, and it can be non-invasively measured with arterial spin labelling (ASL) MRI. In this study, we evaluated and optimized whole-brain, high-resolution ASL as an alternative to the low-resolution ASL employed in the routine assessment of CBF in both healthy participants and patients. Two high-resolution protocols (i.e., pCASL and FAIR-Q2TIPS (PASL) with 2 mm isotropic voxels) were compared to a default clinical pCASL protocol (3.4x3.4x4 mm3), all of whom had an acquisition time of {approx} 5 min. We assessed the impact of high-resolution acquisition on reducing partial voluming and improving sensitivity to the perfusion signal, and evaluated the effectiveness of z-deblurring on the ASL data. We compared the quality of whole-brain ASL acquired using three available head coils with differing numbers of receive channels (i.e., 20, 32, and 64 ch). In conclusion, this study demonstrates the feasibility of high-spatial resolution whole-brain ASL within the clinical scanning duration, offering higher spatial fidelity and resolving power than those obtained with current standard clinical ASL protocols. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551583v1?rss=1 Authors: Guedj, C., Tyrand, R., Badier, E., Planchamp, L., Stringer, M., Zimmermann, M. O., Ferat, V., Ha-Vinh Leuchter, R., Grouiller, F. Abstract: Attention is a crucial cognitive function that enables us to selectively focus on relevant information from the surrounding world to achieve our goals. When this sustained ability to direct attention is impaired, individuals face significant challenges in everyday life. This is the case for children with Attention Deficit Hyperactivity Disorder (ADHD), a complex neurodevelopmental disorder characterized by impulsive and inattentive behavior. While psychostimulant medications are currently the most effective treatment for ADHD, they often come with unwanted side effects, and sustaining the benefits can be difficult for many children. Therefore, it is imperative to explore non-pharmacological treatments that offer longer-lasting outcomes. Here, we proposed a groundbreaking protocol that combines electroencephalography-based neurofeedback (EEG-NFB) with virtual reality (VR) as an innovative approach to treating attention deficits. By integrating a virtual classroom environment, we aimed to enhance the transferability of attentional control skills while simultaneously increasing motivation and interest among children. The present study demonstrated the feasibility of this approach through an initial assessment involving a small group of healthy children, showcasing its potential for future evaluation in children diagnosed with ADHD. Encouragingly, the preliminary findings indicated high engagement rates and positive feedback from the children participating in the study. Additionally, the pre- and post-protocol assessments using EEG and fMRI recordings appeared to converge towards an improvement in attentional function. Although further validation is required to establish the efficacy of the proposed protocol, it represents a significant advancement in the field of neurofeedback therapy for ADHD. The integration of EEG-NFB and VR presents a novel avenue for enhancing attentional control and addressing behavioral challenges in children with ADHD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551607v1?rss=1 Authors: Jiang, S., Chen, L., Qu, W.-M., Huang, Z.-L., Chen, C.-R. Abstract: General anesthetics benefit patients undergoing surgeries without consciousness, but the undesired stress response associated with general anesthesia (GA) causes delayed recovery and even increased morbidity in the clinic. Here, a core hypothalamic ensemble, corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVHCRH neurons) is discovered, which regulates the anesthetic effects and post-anesthesia stress response of sevoflurane GA. Chemogenetic activation of these neurons delay the induction of and accelerated emergence from sevoflurane GA, whereas chemogenetic inhibition exert the opposite effects. Moreover, optogenetic stimulation of PVHCRH neurons induce rapid cortical activation during both the steady and deep sevoflurane GA state with burst-suppression oscillations. Interestingly, chemogenetic inhibition of PVHCRH neurons relieve the sevoflurane GA-elicited stress response (e.g., excessive self-grooming and elevated corticosterone level). These findings identify a common neural substrate integrating the anesthetic effect and post-anesthesia stress response of sevoflurane GA. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551631v1?rss=1 Authors: Hahn, A., Reed, M. B., Vraka, C., Godbersen, G. M., Klug, S., Komorowski, A., Falb, P., Nics, L., Traub-Weidinger, T., Hacker, M., Lanzenberger, R. Abstract: Positron emission tomography (PET) provides precise molecular information on physiological processes, but its low temporal resolution is a major obstacle. Consequently, we characterized the metabolic response of the human brain to working memory performance using an optimized functional PET framework at a temporal resolution of 3 seconds. Consistent with simulated kinetic modeling, we observed a constant increase in the [18F]FDG signal during task execution, followed by a rapid return to baseline after stimulation ceased. The simultaneous acquisition of BOLD fMRI revealed that the temporal coupling between hemodynamic and metabolic signals in the primary motor cortex was related to individual behavioral performance during working memory. Furthermore, task-induced BOLD deactivations in the posteromedial default mode network were accompanied by distinct temporal patterns in glucose metabolism, which depended on the task-positive network metabolic demands. In sum, the proposed approach enables the advancement from parallel to truly synchronized investigation of metabolic and hemodynamic responses during cognitive 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/2023.08.03.551859v1?rss=1 Authors: Di Antonio, G., Raglio, S., Mattia, M. Abstract: A general mathematical description of the way the brain encodes ordinal knowledge of sequences is still lacking. Coherently with the well-established idea of mixed selectivity in high-dimensional state spaces, we conjectured the existence of a linear solution for serial learning tasks. In this theoretical framework, the neural representation of the items in a sequence are read out as ordered projections along a suited "geometric" mental line learned via classical conditioning (delta rule learning). We show that the derived model explains all the behavioral effects observed in humans and other animal species performing the transitive inference task in presence of noisy sensory information and stochastic neural activity. This result is generalized to the case of recurrent neural networks performing motor decision, where the same geometric mental line is learned showing a tight correlation with the motor plan of the responses. Network activity is then eventually modulated according to the symbolic distance of presented item pairs, as observed in associative cortices of nonhuman primates. Serial ordering is thus predicted to emerge as a linear mapping between sensory input and behavioral output, highlighting a possible pivotal role of motor-related associative cortices in the transitive inference task. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.552059v1?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/2023.08.03.551865v1?rss=1 Authors: Turpin, T., Uluc, I., Lankinen, K., Mamashli, F., Ahveninen, J. Abstract: Working memory (WM) reflects the transient maintenance of information in the absence of external input, which can be attained via multiple senses separately or simultaneously. Pertaining to WM, the prevailing literature suggests the dominance of vision over other sensory systems. However, this imbalance may be attributed to challenges of finding stimuli that are represented in comparable ways across modalities. Here, we addressed this methodological problem by using a balanced multisensory "retro-cue" WM design. The to-be-memorized stimuli consisted of combinations of auditory (ripple sounds) and visuospatial (Gabor patches) patterns, which have been shown to undergo similar transformations during WM encoding and retrieval. Using a staircase procedure, the auditory ripple velocities and spatial frequencies of Gabor patches were adjusted relative to each participant's just noticeable differences (JND) separately in each modality, before the main task. The task was to audiovisually compare the probes to the memorized items. In randomly ordered trials, the probe either fully matched or differed from the memory item auditorily, visually, or audiovisually. The participants correctly rejected a significantly larger number of auditory non-match probes than visual non-match probes. Our findings suggest that, in the case of inter-sensory competition during feature maintenance, auditory attributes of multisensory WM items can be retrieved more precisely than their visual counterparts when complexity of the content and task demands are bimodally equated. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.551950v1?rss=1 Authors: Goupell, M. J., Stecker, G. C., Williams, B. T., Bilokon, A., Tollin, D. J. Abstract: The interaural time difference (ITD) is a primary horizontal-plane sound localization cue computed in the auditory brainstem. ITDs are accessible in the temporal fine structure of pure tones with a frequency of no higher than about 1400 Hz. Explaining how listeners' ITD sensitivity transitions from very best sensitivity near 700 Hz to impossible to detect within 1 octave currently lacks a clear physiological explanation. Here, it was hypothesized that the rapid decline in ITD sensitivity is dictated not to a central neural limitation but by initial peripheral sound encoding, specifically, the low-frequency edge of the cochlear excitation pattern produced by a pure tone. To test this hypothesis, ITD sensitivity was measured in 16 normal-hearing listeners as a joint function of frequency (900-1500 Hz) and level (10-50 dB sensation level). Performance decreased with increasing frequency and decreasing sound level. The slope of performance decline was 90 dB/octave, consistent with the low-frequency slope of the cochlear excitation pattern. Consequently, fine-structure ITD sensitivity near 1400 Hz may be conveyed primarily by "off-frequency" activation of neurons tuned to lower frequencies near 700 Hz. Physiologically, this could be realized by a single narrow channel near 700 Hz that conveys fine-structure ITDs. Such a model is a major simplification and departure from the classic formulation of the binaural display, which consists of a matrix of neurons tuned to a wide range of relevant frequencies and ITDs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.551937v1?rss=1 Authors: Luciani, M., Garsia, C., Beretta, S., Petiti, L., Peano, C., Merelli, I., Cifola, I., Miccio, A., Meneghini, V., Gritti, A. Abstract: Human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NSCs) are a promising source for cell therapy approaches to treat neurodegenerative and demyelinating disorders. Despite ongoing efforts to characterize hiPSC-derived cells in vitro and in vivo, we lack comprehensive genome- and transcriptome-wide studies addressing hiPSC-NSC identity and safety, which are critical for establishing accepted criteria for prospective clinical applications. Here, we evaluated the transcriptional and epigenetic signatures of hiPSCs and differentiated hiPSC-NSC progeny, finding that the hiPSC-to-NSC transition results in a complete loss of pluripotency and the acquisition of a radial glia-associated transcriptional signature. Importantly, hiPSC-NSCs share with somatic human fetal NSCs (hfNSCs) the main transcriptional and epigenetic patterns associated with NSC-specific biology. In vivo, long-term observation (up to 10 months) of mice intracerebrally transplanted as neonates with hiPSC-NSCs showed robust engraftment and widespread distribution of human cells in the host brain parenchyma. Engrafted hiPSC-NSCs displayed multilineage potential and preferentially generated glial cells. No hyperproliferation, tumor formation, or expression of pluripotency markers was observed. Finally, we identified a novel role of the Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1) in the regulation of astroglial commitment of hiPSC-NSCs. Overall, these comprehensive in vitro and in vivo analyses provide transcriptional and epigenetic reference datasets to define the maturation stage of NSCs derived from different hiPSC sources, and to clarify the safety profile of hiPSC-NSCs, supporting their continuing development as an alternative to somatic hfNSCs in treating neurodegenerative and demyelinating 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/2023.08.03.551861v1?rss=1 Authors: Kerstein, P. C., Santana Agreda, Y., Curran, B. M., Ma, L., Wright, K. M. Abstract: Within the neuronal classes of the retina, amacrine cells (ACs) exhibit the greatest neuronal diversity in morphology and function. We show that the selective expression of the transcription factor Gbx2 is required for cell fate specification and dendritic stratification of an individual AC subtype in the mouse retina. We identify Robo1 and Robo2 as downstream effectors that when deleted, phenocopy the dendritic misprojections seen in Gbx2 mutants. Slit1 and Slit2, the ligands of Robo receptors, are localized to the OFF layers of the inner plexiform layer where we observe the dendritic misprojections in both Gbx2 and Robo1/2 mutants. We show that Robo receptors also are required for the proper dendritic stratification of additional AC subtypes, such as Vglut3+ ACs. These results show both that Gbx2 functions as a terminal selector in a single AC subtype and identify Slit-Robo signaling as a developmental mechanism for ON-OFF pathway segregation in the retina. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551886v1?rss=1 Authors: Vo, V. A., Jain, S., Beckage, N., Chien, H.-Y. S., Obinwa, C., Huth, A. G. Abstract: Deep learning advances have revolutionized computational modeling approaches in neuroscience. However, their black-box nature makes it challenging to use deep learning models to discover new insights about brain function. Focusing on human language processing, we propose a new framework to improve the quality and interpretability of the inferences we make from deep learning-based models. First, we add interpretable components to a deep language model and use it to build a predictive encoding model. Then, we use the model's predictive abilities to simulate brain responses to controlled stimuli from published experiments. We find that our model, based on a multi-timescale recurrent neural network, captures many previously reported temporal context effects in human cortex. Its failure to capture other effects also highlights important gaps in current language models. Finally, we use this new framework to generate model-based evidence that supports the proposal that different linguistic features are represented at different timescales across cortex. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551829v1?rss=1 Authors: Berto, M., Reisinger, P., Ricciardi, E., Weisz, N., Bottari, D. Abstract: The processing of stationary sounds relies on both local features and compact representations. As local information is compressed into summary statistics, abstract representations emerge. Whether the brain is endowed with distinct neural architectures overseeing such computations is unknown. In this magnetoencephalography (MEG) study, we employed a validated protocol to localize cortical correlates of local and summary representations, exposing participants to triplets of synthetic sound textures systematically varying for either local details or summary statistics. Sounds also varied for their sound duration, specifically short (40ms) or long (478ms). Results revealed clear distinct activation patterns for local features and summary statistics changes. Such activations diverged in magnitude, spatiotemporal distribution, and hemispheric lateralization. For short sounds, a change in local features, compared to summary statistics, predominantly activated the right hemisphere. Conversely, for long sounds, a change in summary statistics elicited higher activation than a change in local features in both hemispheres. Specifically, while the right auditory cortex was responding more to changes in local features or summary statistics depending on sound duration (short or long, respectively), the left frontal lobe was selectively engaged in processing a change in summary statistics at a long sound duration. These findings provide insights into the neural mechanisms underlying the computation of local and summary acoustic information and highlight the involvement of distinct cortical pathways and hemispheric lateralization in auditory processing at different temporal resolutions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.551983v1?rss=1 Authors: Schnupp, J. W., Buchholz, S., Buck, A. N., Budig, H. K., Khurana, L., Rosskothen-Kuhl, N. Abstract: Cochlear implants (CIs) have restored enough of a sense of hearing to around one million severely hearing impaired patients to enable speech understanding in quiet. However, several aspects of hearing with CIs remain very poor. This includes a severely limited ability of CI patients to make use of interaural time difference (ITD) cues for spatial hearing and noise reduction. A major cause for this poor ITD sensitivity could be that current clinical devices fail to deliver ITD information in a manner that is accessible to the auditory pathway. CI processors measure the envelopes of incoming sounds and then stimulate the auditory nerve with electrical pulse trains which are amplitude modulated to reflect incoming sound envelopes. The timing of the pulses generated by the devices is largely or entirely independent of the incoming sounds. Consequently, bilateral CIs (biCIs) provide veridical envelope (ENV) ITDs but largely or entirely replace the "fine structure" ITDs that naturally occur in sounds with completely arbitrary electrical pulse timing (PT) ITDs. To assess the extent to which this matters, we devised experiments that measured the sensitivity of deafened rats to precisely and independently controlled PT and ENV ITDs for a variety of different CI pulse rates and envelope shapes. We observed that PT ITDs completely dominate ITD perception, while the sensitivity to ENV ITDs was almost negligible in comparison. This strongly suggests that the confusing yet powerful PT ITDs that contemporary clinical devices deliver to biCI patients may be a major cause of poor binaural hearing outcomes with biCIs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.551953v1?rss=1 Authors: Jimenez-Marin, A., Diez, I., Erramuzpe, A., Stramaglia, S., Bonifazi, P., Cortes, J. M. Abstract: The human brain is an extremely complex network of structural and functional connections that operate at multiple spatial and temporal scales. Investigating the relationship between these multi-scale connections is critical to advancing our comprehension of brain function and disorders. However, accurately predicting structural connectivity from its functional counterpart remains a challenging pursuit. One of the major impediments is the lack of public repositories that integrate structural and functional networks at diverse resolutions. Addressing this issue, we provide open datasets and code enabling the examination of the correspondence between structural and functional connectivities at different scales. We present a module-level strategy that overcomes region-level approaches in understanding the structure-function correspondence. Moreover, we also provide additional resources focused on neuro-genetic associations of module-level network metrics, which present promising opportunities to further advance research in the field of network neuroscience, particularly concerning brain 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/2023.08.04.551972v1?rss=1 Authors: Hunter, I., Coulson, B., Pettini, T., Davies, J. J., Parkin, J., Landgraf, M., Baines, R. A. Abstract: Developing neural circuits are influenced by activity and are especially sensitive to changes in activity during critical periods (CPs) of development. Changes occurring during a CP often become locked-in so that they affect the mature network. Indeed, several neurodevelopmental disorders have been linked to excessive activity during such periods. It is, therefore, important to identify those aspects of neural circuit development that are influenced by neural activity during a CP. In this study, we take advantage of the genetic tractability of Drosophila to show that activity perturbation during an embryonic CP permanently alters properties of the locomotor circuit. Specific changes we identify include increased synchronicity of motoneuron activity, and greater strengthening of excitatory over inhibitory synaptic drive to motoneurons. These changes are sufficient to reduce network robustness, evidenced by increased sensitivity to induced seizure. We also show that we can rescue these changes when increased activity is mitigated by inhibition provided by mechanosensory neurons. Similarly, we demonstrate a dose-dependent relationship between inhibition experienced during the CP, and the extent to which it is possible to rescue the hyperexcitable phenotype characteristic of the parabss mutation. This suggests that developing circuits must be exposed to a properly balanced sum of excitation and inhibition during the CP, to achieve normal mature network function. Our results, therefore, provide novel insight into how activity during a CP shapes specific elements of a circuit, and how activity during this period is integrated to tune neural circuits to the environment in which they will likely function. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.04.551957v1?rss=1 Authors: Hidalgo-Cortes, J., Manas-Ojeda, A., Olucha-Bordonau, F. E., Garcia-Mompo, C., Castillo-Gomez, E. Abstract: Major depression is the most prevalent neuropsychiatric disorder in elderly population, affecting more than 20% individuals over 60 years old, especially women. In this age range, social isolation is a major risk factor for depression. While there is a significant positive association between social isolation and depression in the elderly population, the neurobiological basis of this association is complex and still poorly understood. Evidence from animal models and human studies indicates that neuroplasticity, especially that of limbic brain regions, is impaired in depression but, till date, scarce studies address this question in older population. In this regard, animal models devoid of human cultural connotations represent a crucial tool. In the present study, we investigated the impact of chronic isolation stress (CIS) and a subsequent resocialization period in aged male and female mice (~ 21 months-old), focusing our attention on affective symptoms and the plasticity of parvalbumin-expressing (PV+) neurons in the lateral/basolateral amygdala (LA/BLA). We found that CIS impaired affective behaviour and LA/BLA plasticity only in females. Specifically, CIS induced depressive-like symptoms and decreased the integrity of perineuronal nets (PNN). Resocialization effectively rescued all these impairments. Old males were not affected by CIS but in social conditions showed higher PNN integrity (less plasticity) than females. All together, our results demonstrate that old females are less resilient to CIS than old males and point to the integrity of PNN in the LA/BLA as a key regulator of depressive-like symptoms induced by social isolation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551600v1?rss=1 Authors: Jokura, K., Ueda, N., Guehmann, M., Yanez-Guerra, L. A., Slowinski, P., Wedgwood, K. C., Jekely, G. Abstract: Nitric oxide (NO) produced by nitric-oxide synthase (NOS) is a key regulator of animal physiology. Here we uncover a function for NO in the integration of UV exposure and the gating of a UV-avoidance circuit. We studied UV/violet avoidance mediated by brain ciliary photoreceptors (cPRCs) in larvae of the annelid Platynereis dumerilii. In the larva, NOS is expressed in interneurons (INNOS) postsynaptic to cPRCs. UV stimulation of cPRCs triggers INNOS activation and NO production. NO signals retrogradely to cPRCs to induce their sustained post-stimulus activation through an unconventional guanylate cyclase. This late activation inhibits serotonergic ciliomotor neurons to induce downward swimming. In NOS mutants, retrograde signalling, circuit output and UV avoidance are defective. By mathematical modelling, we recapitulate phototransduction and circuit dynamics in wild-type and mutant larvae. Our results reveal how NO-mediated retrograde signalling gates a synaptic circuit and induces short-term memory of UV exposure to orchestrate light-avoidance behaviour. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551788v1?rss=1 Authors: Eberhardt, F. Abstract: The cable equation is key for understanding the electrical potential along dendrites or axons, but its application to dendritic spines remains limited. Their volume is extremely small so that moderate ionic currents suffice to alter ionic concentrations. The resulting chemical-potential gradients between dendrite and spine head lead to measurable electrical currents. The cable equation, however, considers electrical currents only as result of gradients in the electrical potential. The Poisson-Nernst-Planck (PNP) equations allow a more accurate description, as they include both types of currents. Previous PNP simulations predict a considerable change of ionic concentrations in spines during an excitatory postsynaptic potential (EPSP). However, solving PNP-equations is computationally expensive, limiting their applicability for complex structures. Here, we present a system of equations that generalizes the cable equation and considers both, electrical potentials and time-dependent concentrations of ion species with individual diffusion constants. Still, basic numerical algorithms can be employed to solve such systems. Based on simulations, we confirm that ion concentrations in dendritic spines are changing significantly during current injections that are comparable to synaptic events. Electrical currents reflecting ion diffusion through the spine neck increase voltage depolarizations in the spine head. Based on this effect, we identify a mechanism that affects the influx of Ca2+ in sequences of pre- and postsynaptic action potentials. Taken together, the diffusion of individual ion species need to be taken into account to accurately model electrical currents in dendritic spines. In the future the presented equations can be used to accurately integrate dendritic spines into multicompartment models to study synatptic 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/2023.08.03.551869v1?rss=1 Authors: Goldman, J. S., Sacha, M., kusch, l., Destexhe, A. Abstract: Thanks to the availability of connectome data that map connectivity between multiple brain areas, it is now possible to build models of whole brain activity. At the same time, advances in mean-field techniques have led to biologically based population models that integrate biophysical features such as membrane conductances or synaptic conductances. In this paper, we show that this approach can lead to brain-wide models of mouse, macaque, and human. We illustrate this approach by showing the transition from wakefulness to sleep simulated with multi-scale models in the three species. We compare the level of synchrony between the three species and found that the mouse brain displays a higher overall synchrony of slow-waves compared to monkey and human brains. We also make the program code publicly available, which provides a set of open-source tools for simulating large-scale activity in the cerebral cortex of mouse, monkey, and human. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551532v1?rss=1 Authors: Qiao, M. Abstract: Understanding how different neuronal types connect and communicate is critical to interpreting brain function and behavior. However, it has remained a formidable challenge to decipher the genetic underpinnings that dictate the specific connections formed between pre- and post-synaptic neuronal types. To address this, we propose a novel bilinear modeling approach that leverages the architecture similar to that of recommendation systems. Our model transforms the gene expressions of mouse bipolar cells (presynaptic) and retinal ganglion cells (postsynaptic), obtained from single-cell transcriptomics, into a covariance matrix. The objective is to construct this covariance matrix that closely mirrors a connectivity matrix, derived from connectomic data, reflecting the known anatomical connections between these neuronal types. Our model successfully recaptiulates recognized connectivity motifs and provides interpretable insights into genetic interactions that shape the connectivity. Specifically, it identifies unique genetic signatures associated with different connectivity motifs, including genes important to cell-cell adhesion and synapse formation, highlighting their role in orchestrating specific synaptic connections between these neurons. Our work establishes an innovative computational strategy for decoding the genetic programming of neuronal type connectivity. It not only sets a new benchmark for single-cell transcriptomic analysis of synaptic connections but also paves the way for mechanistic studies of neural circuit assembly and genetic manipulation of circuit wiring. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551431v1?rss=1 Authors: Misselhorn, J., Fiene, M., Radecke, J.-O., Engel, A. K., Schneider, T. R. Abstract: Attentional control over sensory processing has been linked to neural alpha oscillations and related pulsed inhibition of the human cortex. Despite the wide consensus on the functional relevance of alpha oscillations for attention, precise neural mechanisms of how alpha oscillations shape perception and how this top-down modulation is implemented in cortical networks remain unclear. Here, we tested the hypothesis that alpha oscillations in premotor cortex are causally involved in top-down regulation of visual cortex responsivity to contrast. We applied intermittent transcranial alternating current stimulation (tACS) over bilateral premotor cortex to manipulate attentional preparation in a visual discrimination task. tACS was applied at 10 Hz (alpha) and controlled with 40 Hz (gamma) and sham stimulation. Importantly, we used a novel linear mixed modeling approach for statistical control of neurosensory side-effects of the electric stimulation. We found a frequency-specific effect of alpha tACS on the slope parameter, leading to enhanced low-contrast perception and decreased perception of high-contrast stimuli. Side-effects affected both threshold and slope parameters, leading to high variability in parameter estimates. Controlling the impact of side-effects on psychometric parameters by linear mixed model analysis reduced variability and clarified the existing effect. We conclude that alpha tACS over premotor cortex mimicked a state of increased endogenous attention potentially by modulation of fronto-occipital connectivity in the alpha band. We speculate that this network modulation allowed for improved sensory readout from visual cortex which led to a decrease in psychometric slope, effectively broadening the dynamic range for contrast perception. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551412v1?rss=1 Authors: Gladhill, K., De Kock, R., Zhou, W., Joiner, W. M., Wiener, M. Abstract: Contemporary research has begun to show a strong relationship between movements and the perception of time. More specifically, concurrent movements serve to both bias and enhance time estimates. To explain these effects, we recently proposed a mechanism by which movements provide a secondary channel for estimating duration that is combined optimally with sensory estimates, in accordance with Bayesian cue combination. However, a critical test of this framework is that by introducing "noise" into movements, sensory estimates of time should similarly become noisier in a manner predicted by cue combination equations. To accomplish this, we had human participants move a robotic arm while estimating intervals of time in either auditory or visual modalities (n=24, ea.). Crucially, we introduced an artificial "tremor" in the arm while subjects were moving, that varied across three levels of amplitude (1-3 N) or frequency (4-12 Hz). The results of both experiments revealed that increasing the frequency of the tremor led to noisier estimates of duration, but in such a way that higher levels of noise saturated the impact, consistent with optimal integration. Further, the effect of noise varied with the base precision of the interval, such that a naturally less precise timing (i.e. visual) was more influenced by the tremor than a naturally more precise modality (i.e. auditory). To explain these findings, we fit the data with a recently developed drift-diffusion model of perceptual decision making, in which the momentary, within-trial variance was allowed to vary across conditions. Here, we found that the model could recapitulate the observed findings, further supporting the theory that movements influence perception directly. Overall, our findings support the proposed framework, and demonstrate the utility of inducing motor noise via artificial tremors, thus providing clinical utility in their connection to movement disorders characterized by tremors. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551808v1?rss=1 Authors: Ribeiro, F. C., Cozachenco, D., Argyrousi, E. K., Staniszewski, A., Wiebe, S., Calixtro, J. D., Soares-Neto, R., Al-Chami, A., El Sayegh, F., Bermudez, S., Arsenault, E., Cossenza, M., Lacaille, J.-C., Nader, K., Sun, H., De Felice, F. G., Lourenco, M. V., Arancio, O., Aguilar-Valles, A., Sonenberg, N., Ferreira, S. T. Abstract: Impaired synaptic plasticity and progressive memory deficits are major hallmarks of Alzheimer's disease (AD). Hippocampal mRNA translation, required for memory consolidation, is defective in AD. Here, we show that genetic reduction of the translational repressors, Fragile X messenger ribonucleoprotein (FMRP) or eukaryotic initiation factor 4E (eIF4E)-binding protein 2 (4E-BP2), ameliorated the inhibition of hippocampal protein synthesis and memory impairment induced by AD-linked amyloid-b; oligomers (AbOs) in mice. Furthermore, systemic treatment with (2R,6R)-hydroxynorketamine (HNK), an active metabolite of the antidepressant ketamine, prevented deficits in hippocampal mRNA translation, long-term potentiation (LTP) and memory induced by AbOs in mice. HNK activated hippocampal signaling by extracellular signal-regulated kinase 1/2 (ERK1/2), mechanistic target of rapamycin (mTOR), and p70S6 kinase 1 (S6K1)/ribosomal protein S6 (S6), which promote protein synthesis and synaptic plasticity. S6 phosphorylation instigated by HNK was mediated by mTOR in hippocampal slices, while rescue of hippocampal LTP and memory in HNK-treated AbO-infused mice depended on ERK1/2 and, partially, on mTORC1. Remarkably, treatment with HNK corrected LTP and memory deficits in aged APP/PS1 mice. RNAseq analysis showed that HNK reversed aberrant signaling pathways that are upregulated in APP/PS1 mice, including inflammatory and hormonal responses and programmed cell death. Taken together, our findings demonstrate that upregulation of mRNA translation corrects deficits in hippocampal synaptic plasticity and memory in AD models. The results raise the prospect that HNK could serve as a therapeutic to reverse memory decline in AD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551513v1?rss=1 Authors: de Haas, N., Ottink, L., Doeller, C. Abstract: The hippocampus is a key region for forming mental maps of our environment. These maps represent spatial information such as distances between landmarks. A cognitive map can allow for flexible inference of spatial relationships that have never been directly experienced before. Previous work has shown that the human hippocampus encodes distances between locations, but it is unclear how Euclidean and path distances are distinguished. In this study, participants performed an object-location task in a virtual environment. We combined functional magnetic resonance imaging with representational similarity analysis to test how Euclidean and path distances are represented in the hippocampus. We observe that hippocampal neural pattern similarity for objects scales with Euclidean as well as path distance between object locations, suggesting that the hippocampus integrates both types of distances. One key characteristic of cognitive maps is their adaptive and flexible nature. We therefore subsequently modified path distances between objects using roadblocks in the environment. We found that hippocampal pattern similarity between objects adapted as a function of these changes in path distance, selectively in egocentric navigators but not in allocentric navigators Taken together, our study supports the idea that the hippocampus creates integrative and flexible cognitive maps. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551710v1?rss=1 Authors: Antonoudiou, P., Stone, B., Colmers, P., Evans-Strong, A., Walton, N., Weiss, G., Maguire, J. Abstract: The basolateral amygdala (BLA) is an emotional processing hub and is well-established to influence both positive and negative valence processing. Selective engagement of a heterogeneous cell population in the BLA is thought to contribute to this flexibility in valence processing. However, how this process is impacted by previous experiences which influence valence processing is unknown. Here we demonstrate that previous positive (EE) or negative (chronic unpredictable stress) experiences differentially influence the activity of specific populations of BLA principal neurons projecting to either the nucleus accumbens core or bed nucleus of the stria terminalis. Using chemogenetic manipulation of these projection-specific neurons we can mimic or occlude the effects of chronic unpredictable stress or enriched environment on valence processing to bidirectionally control avoidance behaviors and stress-induced helplessness. These data demonstrate that previous experiences influence the responsiveness of projection-specific BLA principal neurons, biasing information routing through the BLA, to govern valence 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/2023.08.03.551520v1?rss=1 Authors: Duecker, K., Shapiro, K., Hanslmayr, S., Wolfe, J., Pan, Y., Jensen, O. Abstract: Visual search models have long emphasised that task-relevant items must be prioritized for optimal performance. While it is known that search efficiency also benefits from active distractor inhibition, the underlying neuronal mechanisms are debated. Here, we used MEG in combination with Rapid Invisible Frequency Tagging (RIFT) to understand the neural correlates of feature-guided visual search. RIFT served as a continuous read-out of the neuronal excitability to the search stimuli and revealed evidence for target boosting and distractor suppression in early visual cortex. These findings were complemented by an increase in occipital alpha power predicting faster responses and higher hit rates, as well as reduced RIFT responses to all stimuli, regardless of their task-relevance. We propose that alpha oscillations in early visual regions implement a blanket inhibition that reduces neuronal excitability to both target and distractor features. As the excitability of neurons encoding the target features is boosted, these neurons overcome the inhibition, facilitating guidance towards task-relevant stimuli. Our results provide novel insights on a mechanism in early visual regions that supports selective attention through inhibition. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.548378v1?rss=1 Authors: Nitsch, A., Garvert, M. M., Bellmund, J. L. S., Schuck, N. W., Doeller, C. F. Abstract: Everyday decisions require us to predict how valuable different choice options will be in the future. Prior studies have identified a cognitive map in the hippocampal-entorhinal system that encodes relationships between states and enables prediction of future states, but does not inherently convey value during prospective decision making. Here, we investigated whether the entorhinal cortex integrates relational information about changing values by representing an abstract value space. To this end, we combined fMRI with a prospective decision making task that required participants to track and predict changing values of two choice options in a sequence. Such a sequence formed a trajectory through an underlying two-dimensional value space. Our results show that participants successfully integrated and extrapolated changes along the two value dimensions. Participants' choice behavior was explained by a prospective reinforcement learning model and the degree to which they updated values over time correlated with self-reported navigational abilities and preferences. Crucially, while participants traversed the abstract value space, the entorhinal cortex exhibited a grid-like representation, with the phase of the hexadirectional fMRI signal (i.e., the orientation of the estimated grid) being aligned to the most informative axis through the value space. A network of brain regions, including the ventromedial prefrontal cortex (vmPFC), tracked the prospective value difference between options and the occipital-temporal cortex represented the more valuable option. These findings suggest that the entorhinal grid system might support the prediction of future values by representing a cognitive map, which might be used to generate lower-dimensional signals of the value difference between options and their identities for choices. Thus, these findings provide novel insight for our understanding of cognitive maps as a mechanism to guide prospective decision making in humans. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551676v1?rss=1 Authors: Wu, P. Y., Ji, L., De Sanctis, C., Francesconi, A., Inglebert, Y., McKinney, R. A. Abstract: Metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) is an important form of synaptic plasticity that occurs in many regions of the CNS and is the underlying mechanism for several learning paradigms. In the hippocampus, mGluR-LTD is manifested by the weakening of synaptic transmission and elimination of dendritic spines. Interestingly, not all spines respond or undergo plasticity equally in response to mGluR-LTD. A subset of dendritic spines containing synaptopodin (SP), an actin-associated protein, are critical for mGluR-LTD and protect spines from elimination through mGluR1 activity. The precise cellular function of SP is still enigmatic and it is still unclear how SP contributes to the functional aspect of mGluR-LTD despite of its modulation on the structural plasticity. In the present study, we show that the lack of SP impairs mGluR-LTD by negatively affecting the mGluR5-dependent activity. Such impairment of mGluR5 activity is accompanied by a significant decrease of surface mGluR5 level in SP knockout (SPKO) mice. Intriguingly, the remaining mGluR-LTD becomes a protein synthesis-independent process in the SPKO and is mediated instead by endocannabinoid signaling. These data show for the first time that the postsynaptic protein SP can regulate the locus of expression of mGluR-LTD and provide insight to our understanding of spine/synapse-specific plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551642v1?rss=1 Authors: Anderson, E. D., Varshney, L. R., Hemmatian, B., Robles-Granda, P. D., Nayak, A. K., Wilcox, R. R., Zwilling, C. E., Kim, B., Barbey, A. K. Abstract: Research in network neuroscience demonstrates that human intelligence is shaped by the structural brain connectome, which enables a globally coordinated and dynamic architecture for general intelligence. Building on this perspective, the network neuroscience theory proposes that intelligence arises from system-wide network dynamics and the capacity to flexibly transition between network states. According to this view, network flexibility is made possible by network controllers that move the system into specific network states, enabling solutions to familiar problems by accessing nearby, easy-to-reach network states and adapting to novel situations by engaging distant, difficult-to-reach network states. Although this framework predicts that general intelligence depends on network controllability, the specific cortical regions that serve as network controllers and the nature of their control operations remain to be established. We therefore conducted a comprehensive investigation of the relationship between regional measures of network controllability and general intelligence within a sample of 275 healthy young adults using structural and diffusion-weighted MRI data. Our findings revealed significant associations between intelligence and network controllers located within the frontal, temporal and parietal cortex. Furthermore, we discovered that these controllers collectively enable access to both easy- and difficult-to-reach network states, aligning with the predictions made by the network neuroscience framework. Additionally, our research demonstrated that the identified network controllers are primarily localized within the left hemisphere and do not reside within regions or connections that possess the highest capacity for structural control in general. This discovery suggests that the identified regions may facilitate specialized control operations and motivates further exploration of the network topology and dynamics underlying intelligence in the human brain. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.02.551645v1?rss=1 Authors: Shepard, N., Baez-Nieto, D., Iqbal, S., Campbell, A. J., Pan, J. Q., Sheng, M., Farsi, Z. Abstract: Human genetic studies have revealed rare missense and protein-truncating variants in GRIN2A, encoding for the GluN2A subunit of the NMDA receptors, that confer significant risk for schizophrenia (SCZ). Mutations in GRIN2A are also associated with epilepsy and developmental delay/intellectual disability (DD/ID). However, it remains enigmatic how alterations to the same protein can result in diverse clinical phenotypes. Here, we performed functional characterization of human NMDA receptors (GluN1/GluN2A heteromers) that contain SCZ-linked GluN2A variants, and compared them to NMDA receptors with GluN2A variants associated with epilepsy or DD/ID. All tested protein-truncating variants and a subset of missense variants associated with SCZ led to a loss-of-function (LoF) phenotype, whereas epilepsy and DD/ID-associated variants resulted in both gain- and loss-of-function phenotypes. We additionally show that M653I, a LoF GRIN2A variant associated with DD/ID, exerts a dominant-negative effect when co-expressed with a wild-type GluN2A, whereas Y698C, a LoF SCZ-linked variant, does not. These findings demonstrate that SCZ-associated GRIN2A variants are predominantly LoF and offer a potential mechanism by which SCZ and DD/ID-linked variants can cause different effects on receptor function and therefore result in divergent pathological outcomes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551291v1?rss=1 Authors: Hamilton, L. K., Mbra, P. E. H., Mailloux, S., Galoppin, M., Aumont, A., Fernandes, K. J. L. Abstract: Evidence from genetic and epidemiological studies point to lipid metabolism defects in both the brain and periphery being at the core of Alzheimer's disease (AD) pathogenesis. Previously, we reported that central inhibition of the rate-limiting enzyme in monounsaturated fatty acid synthesis, Stearoyl-CoA Desaturase (SCD), improves brain structure and function in the 3xTg mouse model of AD. Here, we tested whether these beneficial central effects involve recovery of peripheral metabolic defects, such as fat accumulation and glucose and insulin handling. As early as 3 months of age, 3xTg-AD mice exhibited obesity-like phenotypes including increased body weight and visceral and subcutaneous white adipose tissue deposition, as well as diabetic-like peripheral gluco-regulatory abnormalities. Intracerebral infusion of an SCD inhibitor that normalizes brain fatty acid metabolism, synapse loss and learning and memory deficits in middle-aged symptomatic 3xTg-AD mice did not affect peripheral phenotypes. This suggests that the beneficial effects of central SCD inhibition on cognitive function are not mediated by recovery of peripheral metabolic abnormalities. Given the widespread side-effects of systemically administered SCD inhibitors, these data suggest that selective inhibition of SCD in the brain may represent a clinically safer and more effective strategy for AD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551579v1?rss=1 Authors: Sanghavi, S., Kar, K. Abstract: A spatially distributed population of neurons in the macaque inferior temporal (IT) cortex supports object recognition behavior, but the cell-type specificity of the population in forming behaviorally sufficient object decodes remain unclear. To address this, we recorded neural signals from the macaque IT cortex and compared the object identity information and the alignment of decoding strategies derived from putative inhibitory (Inh) and excitatory (Exc) neurons to the monkeys' behavior. We observed that while Inh neurons represented significant category information, decoding strategies based on Exc neural population activity outperformed those from Inh neurons in overall accuracy and their image-level match to the monkeys' behavioral reports. Interestingly, both Exc and Inh responses explained a fraction of unique variance of the monkeys' behavior, demonstrating a distinct role of the two cell types in generating object identity solutions for a downstream readout. We observed that current artificial neural network (ANN) models of primate ventral stream, designed with AI goals of performance optimization on image categorization, better predict Exc neurons (and its contribution to object recognition behavior) than Inh neurons. Beyond, the refinement of linking propositions between IT and object recognition behavior, our results guide the development of more biologically constrained brain models by offering novel cell-type specific neural benchmarks. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551587v1?rss=1 Authors: Plagwitz, L., Choi, S., Yu, X., Segelcke, D., Pogatzki-Zahn, E. M., Varghese, J., Faber, C., Pradier, B. Abstract: The analysis of large data sets within and across preclinical studies has always posed a particular challenge in terms of data volume and method heterogeneity between studies. Recent developments in machine learning (ML) and artificial intelligence (AI) allow to address these challenges in complex macro- and microscopic data sets. Because of their complex data structure, functional magnetic resonance imaging (fMRI) measurements are perfectly suited to develop such ML/AI frameworks for data-driven analyses. These approaches have the potential to reveal patterns, including temporal kinetics, in blood-oxygen-level-dependent (BOLD) time series with a reduced workload. However, the typically poor signal-to-noise ratio (SNR) and low temporal resolution of fMRI time series have so far hampered such advances. Therefore, we used line scanning fMRI measurements with high SNR and high spatio-temporal resolution obtained from three independent studies and two imaging centers with heterogeneous study protocols. Unbiased time series clustering techniques were applied for the analysis of somatosensory information processing during electrical paw and optogenetic stimulation. Depending on the similarity formulation, our workflow revealed multiple patterns in BOLD time series. It produced consistent outcomes across different studies and study protocols, demonstrating the generalizability of the data-driven method for cross-study analyzes. Further, we introduce a statistical analysis that is entirely based on cluster distribution. Using this method, we can reproduce previous findings including differences in temporal BOLD characteristics between two stimulation modalities. Our data-driven approach proves high sensitivity, robustness, reproducibility, and generalizability and further quickly provides highly detailed insight into characteristics of BOLD time series. Therefore, it holds great potential for further applications in fMRI data including whole-brain task and resting-state fMRI, which can support fMRI routines. Furthermore, the analytic framework can be used for datasets that have a time-dependent data structure to integrate study results and create robust and generalizable datasets, despite different study protocols. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551248v1?rss=1 Authors: Baraibar, A. M., Colomer, T., Moreno-Garcia, A., Bernal-Chico, A., Sanchez, E., Utrilla, C., Serrat, R., Soria-Gomez, E., Rodriguez-Antiguedad, A., Araque, A., Matute, C., Marsicano, G., Mato, S. Abstract: Cortical pathology involving inflammatory and neurodegenerative mechanisms is a hallmark of multiple sclerosis (MS) and a correlate of disease progression and cognitive decline. Astrocytes play a pivotal role in MS initiation and progression but astrocyte-neuronal network alterations contributing to gray matter pathology remain undefined. Here we measured astrocytic calcium in the experimental autoimmune encephalomyelitis (EAE) model of MS using fiber photometry in freely behaving mice and two-photon imaging ex vivo. We identified the emergence of spontaneously hyperactive cortical astrocytes displaying calcium transients of increased duration as well as dysfunctional responses to cannabinoid, glutamate and purinoreceptor agonists during acute EAE disease. Deficits in astrocyte calcium responses are associated to abnormal signaling by Gi and Gq protein coupled receptors in the inflamed cortex and are partially mirrored in cells activated with pro-inflammatory factors both in vitro and ex vivo thus suggesting cell-autonomous effects of the cortical neuroinflammatory environment. Finally, we show that deregulated astrocyte calcium activity is associated to an enhancement of glutamatergic gliotransmission and a shift of astrocyte-mediated short-term and long-term plasticity mechanisms towards synaptic potentiation. Overall our data identities astrocyte-neuronal network dysfunction as key pathological feature of the inflammatory gray matter that may contribute to MS symptomatology and clinical progression. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551490v1?rss=1 Authors: Akil, A. M., Cserjesi, R., Nemeth, D., Nagy, T., Demetrovics, Z., Logemann, H. N. A. Abstract: Studies have suggested that the asymmetry of frontal brain activity is linked to self-regulation, particularly with approach tendencies in comparison to avoidance tendencies. However, the specific brain mechanism is not clear. Our preregistered study aimed to address the limitations of previous correlational studies by employing an interventional method, specifically non-invasive brain stimulation, regarding the connection between frontal alpha asymmetry (FAA) and the behavioral and brain activity components related to approach tendencies, as observed in a visuospatial cueing (VSC) paradigm. A randomized controlled triple-blind design was used, and the experiment involved 65 participants. During the study, participant EEG was recorded and they performed a VSC task before and after the sham/active tDCS intervention The task included neutral and intrinsic reward-associated (food) conditions. The tDCS intervention consisted of 2 mA current applied to the right frontal F4 (anode) site relative to the left frontal F3 (cathode) site. The results showed no evidence that tDCS had an impact on FAA. There was also no indication of tDCS affecting the behavioral manifestations of attentional bias or disengagement. Surprisingly, secondary analyses concerning event-related potentials revealed that tDCS enhanced both the Late Directing Attention Positivity and P1 effect in the reward context. These findings suggest that tDCS might heighten cue-induced approach tendencies in a reward context, but these effects did not translate into observable behavioral changes. The observed effects are consistent with a noradrenergic mechanism rather than asymmetry of brain activity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551556v1?rss=1 Authors: Almoril-Porras, A., Calvo, A., Niu, L.-G., Beagan, J., Hawk, J. D., Aljobeh, A., Wisdom, E., Ren, I., Diaz-Garcia, M., Wang, Z.-W., Colon-Ramos, D. Abstract: Synaptic configurations in precisely wired circuits underpin how sensory information is processed by the nervous system, and the emerging animal behavior. This is best understood for chemical synapses, but far less is known about how electrical synaptic configurations modulate, in vivo and in specific neurons, sensory information processing and context-specific behaviors. We discovered that INX-1, a gap junction protein that forms electrical synapses, is required to deploy context-specific behavioral strategies during C. elegans thermotaxis behavior. INX-1 couples two bilaterally symmetric interneurons, and this configuration is required for the integration of sensory information during migration of animals across temperature gradients. In inx-1 mutants, uncoupled interneurons display increased excitability and responses to subthreshold temperature stimuli, resulting in abnormally longer run durations and context-irrelevant tracking of isotherms. Our study uncovers a conserved configuration of electrical synapses that, by increasing neuronal capacitance, enables differential processing of sensory information and the deployment of context-specific behavioral strategies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551505v1?rss=1 Authors: Peraza, J. A., Salo, T., Riedel, M. C., Bottenhorn, K. L., Poline, J.-B., Dockes, J., Kent, J. D., Bartley, J. E., Flannery, J. S., Hill-Bowen, L. D., Lobo, R. P., Poudel, R., Ray, K. L., Robinson, J. L., Laird, R. W., Sutherland, M. T., de la Vega, A., Laird, A. R. Abstract: Macroscale gradients have emerged as a central principle for understanding functional brain organization. Previous studies have demonstrated that a principal gradient of connectivity in the human brain exists, with unimodal primary sensorimotor regions situated at one end, and transmodal regions associated with the default mode network and representative of abstract functioning at the other. The functional significance and interpretation of macroscale gradients remains a central topic of discussion in the neuroimaging community, with some studies demonstrating that gradients may be described using meta-analytic functional decoding techniques. However, additional methodological development is necessary to more fully leverage available meta-analytic methods and resources and quantitatively evaluate their relative performance. Here, we conducted a comprehensive series of analyses to investigate and improve the framework of data-driven, meta-analytic methods, thereby establishing a principled approach for gradient segmentation and functional decoding. We found that a small number of segments determined by a K-means segmentation approach and an LDA-based meta-analysis combined with the NeuroQuery database was the optimal combination of methods for decoding functional connectivity gradients. Taken together, the current work aims to provide recommendations on best practices, along with flexible methods, for gradient-based functional decoding of fMRI data. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551503v1?rss=1 Authors: Swanson, K. A., Nguyen, K. L., Gupta, S., Ricard, J., Bethea, J. R. Abstract: Upregulation of soluble tumor necrosis factor (sTNF) cytokine signaling through TNF receptor 1 (TNFR1) and subsequent neuronal hyperexcitability are observed in both animal models and human chronic neuropathic pain (CNP) (Clark et al., 2013; Empl et al., 2001; Ji et al., 2018; Lindenlaub and Sommer, 2003). To test the hypothesis that supraspinal circuitry is critical to pain chronification, we studied the intersect between supraspinal TNFR1 mediated neuronal signaling and sex specificity by selectively removing TNFR1 in Nex+ neurons in adult mice (NexCreERT2::TNFR1f/f). We determined that following chronic constriction injury (CCI), pain resolves in males; however, female acute pain transitions to chronic. Subsequently, we investigated two downstream pathways, p38MAPK and NF-{kappa}B, important in TNFR1 signaling and injury response. We detected p38MAPK and NF- {kappa}B activation in male cortical tissue; however, p38MAPK phosphorylation was reduced in NexCreERT2::TNFR1f/f males. We observed similar behavioral results following CCI in NexCreERT2::p38MAPKf/f mice. Previously, we established estrogen's ability to modulate sTNF/TNFR1 signaling in CNP, which may contribute to female prevalence of CNP (Bouhassira et al., 2008; Claiborne et al., 2006; de Mos et al., 2007; Del Rivero et al., 2019; Li et al., 2009). To explore the intersection between estrogen and inflammation in CNP we used a combination therapy of an estrogen receptor {beta} (ER {beta}) inhibitor with a sTNF/TNFR1 or general p38MAPK inhibitor. We determined both combination therapies lend "male-like" therapeutic relief to females following CCI. These data suggest that TNFR1/p38MAPK signaling in Nex+ neurons in CNP is male-specific and lack of therapeutic efficacy following sTNF inhibition in females is due to ER {beta} interference. These studies highlight sex-specific differences in pathways important to pain chronification and elucidate potential therapeutic strategies that would be effective in both sexes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551506v1?rss=1 Authors: Ren, Y., Brown, T. Abstract: Listening to music during cognitive activities, such as reading and studying, is very common in human daily life. Therefore, it is important to understand how music interacts with concurrent cognitive functions, particularly memory. Current literature has presented mixed results for whether music can benefit learning in other modalities. Evidence is needed for what neural mechanisms music can tap into to enhance concurrent memory processing. This fMRI study aimed to begin filling this gap by investigating how music of varying predictability levels influences parallel visual sequence encoding performance. Behavioral results suggest that overall, predictable music enhances visual sequential encoding, and this effect increases with the structural regularity and familiarity of music. fMRI results indicate that during visual sequence encoding, music activates traditional music-processing and motor-related areas, but decreases parahippocampal and striatal engagement. This deactivation may indicate a more efficient encoding of visual information when music is present. By comparing music conditions of different structural predictability and familiarity, we probed how this occurs. We demonstrate improved encoding with increased syntactical regularity, which was associated with decreased activity in default mode network and increased activity in inferior temporal gyrus. Furthermore, the temporal schema provided by music familiarity may influence encoding through altered functional connectivity between the prefrontal cortex, medial temporal lobe and striatum. Overall, we propose that pairing music with learning might facilitate memory by reducing neural demands for visual encoding and simultaneously strengthening the connectivity between the medial temporal lobe and frontostriatal loops important for sequencing information. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551547v1?rss=1 Authors: Lee, D., Liu, L., Root, C. M. Abstract: The ways in which sensory stimuli acquire motivational valence through association with other stimuli is one of the simplest forms of learning. Though we have identified many brain nuclei that play various roles in reward processing, a significant gap remains in understanding how value encoding transforms through the layers of sensory processing. To address this gap, we carried out a comparative investigation of the olfactory tubercle (OT), and the ventral pallidum (VP) - 2 connected nuclei of the basal ganglia which have both been implicated in reward processing. First, using anterograde and retrograde tracing, we show that both D1 and D2 neurons of the OT project primarily to the VP and minimally elsewhere. Using 2-photon calcium imaging, we then investigated how the identity of the odor and reward contingency of the odor are differently encoded by neurons in either structure during a classical conditioning paradigm. We find that VP neurons robustly encode value, but not identity, in low-dimensional space. In contrast, OT neurons primarily encode odor identity in high-dimensional space. Though D1 OT neurons showed larger response vectors to rewarded odors than other odors, we propose this is better interpreted as identity encoding with enhanced contrast rather than as value encoding. Finally, using a novel conditioning paradigm that decouples reward contingency and licking vigor, we show that both features are encoded by non-overlapping VP neurons. These results provide a novel framework for the striatopallidal circuit in which a high-dimensional encoding of stimulus identity is collapsed onto a low-dimensional encoding of motivational valence. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551482v1?rss=1 Authors: O'Neill, G. C., Seymour, R. A., Mellor, S., Alexander, N., Tierney, T. M., Bernachot, L., Fahimi Hnazee, M., Spedden, M. E., Timms, R. C., Bestmann, S., Brookes, M. J., Barnes, G. R. Abstract: Neuroimaging studies have typically relied on rigorously controlled experimental paradigms to probe cognition, in which movement is primitive, an afterthought or merely used to indicate a subject's choice. Whilst powerful, these paradigms often do not resemble how we behave in everyday life, so a new generation of ecologically valid experiments are being developed. Magnetoencephalography (MEG) measures neural activity by sensing extracranial magnetic fields. It has recently been transformed from a large, static imaging modality to a wearable method where participants can freely move. This makes wearable MEG systems a candidate for naturalistic experiments going forward. Additional measures that capture information about complex behaviours that are compatible with neuroimaging techniques, such as MEG, will benefit researchers therefore needed for naturalistic experiments using naturalistic paradigms. Here we use video data from multi-limb dance moves, processed with open-source machine learning methods, to directly cue the timings of task onset and offset in wearable MEG data In a first step, we compare a traditional, block-designed analysis of limb movements, where the times of interest are based on stimulus presentation, to an analysis pipeline based on hidden Markov model states derived from the video telemetry. We then show that by observing the participants choreographed movement in a dancing paradigm, it is possible to express modes of neuronal activity related to specific limbs and body posture. This demonstrates the potential of combing video telemetry with mobile neuroimaging for future studies of complex and naturalistic behaviours. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551475v1?rss=1 Authors: Ekanayake, A., Yang, Q., Kanekar, S., Ahmed, B., McCaslin, S., Kalra, D., Eslinger, P., Karunanayaka, P. Abstract: The olfactory nerve, also known as cranial nerve I, is known to have exclusive ipsilateral projections to primary olfactory cortical structures. It is still unclear whether these projections also correspond to functional pathways of odor processing. In an olfactory functional magnetic resonance imaging (fMRI) study of twenty young healthy subjects with a normal sense of smell, we tested whether nostril specific stimulation with phenyl ethyl alcohol (PEA), a pure olfactory stimulant, asymmetrically activates primary or secondary olfactory-related brain structures such as primary olfactory cortex, entorhinal cortex, and orbitofrontal cortex. The results indicated that without a challenging olfactory task, passive (no sniffing) and active (with sniffing) nostril-specific PEA stimulation did not produce asymmetrical fMRI activation in olfactory cortical structures. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551512v1?rss=1 Authors: Xu, H., Dugue, G., Cantaut-Belarif, Y., Lejeune, F.-X., Gupta, S., Wyart, C., Lehtinen, M. K. Abstract: Reissner's fiber (RF) is an extracellular polymer comprising the large monomeric protein SCO-spondin (SSPO) secreted by the subcommissural organ (SCO) that extends through cerebrospinal fluid (CSF)-filled ventricles into the central canal of the spinal cord. In zebrafish, RF and CSF-contacting neurons (CSF-cNs) form an axial sensory system that detects spinal curvature, instructs morphogenesis of the body axis, and enables proper alignment of the spine. In mammalian models, RF has been implicated in CSF circulation. However, challenges in manipulating Sspo, an exceptionally large gene of 15,719 nucleotides, with traditional approaches has limited progress. Here, we generated a Sspo knockout mouse model using CRISPR/Cas9-mediated genome-editing. Sspo knockout mice lacked RF-positive material in the SCO and fibrillar condensates in the brain ventricles. Remarkably, Sspo knockout brain ventricle sizes were reduced compared to littermate controls. Minor defects in thoracic spine curvature were detected in Sspo knockouts, which did not alter basic motor behaviors tested. Altogether, our work in mouse demonstrates that SSPO and RF regulate ventricle size during development but only moderately impact spine geometry. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC