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Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, is approved for obesity treatment, but the specific neuronal sites that contribute to its therapeutic effects remain elusive. Here, we show that GLP-1 receptor-positive (GLP-1R-positive) neurons in the lateral septum (LSGLP-1R) play a critical role in mediating the anorectic and weight-loss effects of liraglutide. LSGLP-1R neurons were robustly activated by liraglutide, and chemogenetic activation of these neurons dramatically suppressed feeding. Targeted knockdown of GLP-1 receptors within the LS, but not in the hypothalamus, substantially attenuated liraglutide's ability to inhibit feeding and lower body weight. The activity of LSGLP-1R neurons rapidly decreased during naturalistic feeding episodes, while synaptic inactivation of LSGLP-1R neurons diminished the anorexic effects triggered by liraglutide. Together, these findings offer critical insights into the functional role of LSGLP-1R neurons in the physiological regulation of energy homeostasis and delineate their instrumental role in mediating the pharmacological efficacy of liraglutide.

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Sleep deprivation (SD) has negative effects on brain and body function. Sleep problems are prevalent in a variety of disorders, including neurodevelopmental and psychiatric conditions. Thus, understanding the molecular consequences of SD is of fundamental importance in biology. In this study, we present the first simultaneous bulk and single-nuclear RNA sequencing characterization of the effects of SD in the male mouse frontal cortex. We show that SD predominantly affects glutamatergic neurons, specifically in layers 4 and 5, and produces isoform switching of over 1500 genes, particularly those involved in splicing and RNA binding. At both the global and cell-type specific level, SD has a large repressive effect on transcription, downregulating thousands of genes and transcripts. As a resource we provide extensive characterizations of cell-types, genes, transcripts, and pathways affected by SD. We also provide publicly available tutorials aimed at allowing readers adapt analyses performed in this study to their own datasets.

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Recently, increasing evidence has shown the association between liver abnormal inflammation and cognition impairment, yet their age-related pathogenesis remains obscure. Here, our study provides a potential mechanistic link between liver macrophage excessive activation and neuroinflammation in aging progression. In aged and LPS-injected C57BL/6J mice, systemic administration of ß-chitosan ameliorates hepatic macrophage-driven inflammation and reduces peripheral accumulations of TNF-α and IL-1ß. Downregulation of circulatory pro-inflammatory cytokines then decreases vascular VCAM1 expression and neuroinflammation in the hippocampus, leading to cognitive improvement in aged/LPS-stimulated mice. Interestingly, ß-chitosan treatment also exhibits the beneficial effects on the behavioral recovery of aged/LPS-stimulated zebrafish and Caenorhabditis elegans. In our cell culture and molecular docking experiments, we found that ß-chitosan prefers shielding the MD-2 pocket, thus blocking the activation of TLR4-MD-2 complex to suppress NF-κB signaling pathway activation. Together, our findings highlight the extensive therapeutic potential of ß-chitosan in reversing aged-related/LPS-induced cognitive impairment via the liver-brain axis.

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Cortical interneurons shape network activity in cell type-specific ways, and interact with other cell types. These interactions are understudied, as current methods typically restrict in vivo labeling to one neuron type. Although post-hoc identification of many cell types has been accomplished, the method is not available to many labs. We present a method to distinguish two red fluorophores in vivo, allowing imaging of activity in somatostatin (SOM), parvalbumin (PV), and the rest of the neural population in mouse cortex. We compared population events in PV and SOM neurons and observed that local network states reflected the ratio of SOM to PV neuron activity, demonstrating the importance of simultaneous labeling to explain dynamics. Activity became sparser and less correlated when the ratio between SOM and PV activity was high. Our simple method can be flexibly applied to study interactions among any combination of distinct cell type populations across brain areas.

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Post-laser-assisted in situ keratomileusis (LASIK) corneal ectasia is a severe complication of corneal refractive surgery, and cryopreserved lenticules from hyperopic small incision lenticule extraction (SMILE) may offer a promising treatment though their long-term safety and efficacy are still under investigation. In this prospective case series, six eyes from six patients with post-LASIK ectasia received lenticules (mean cryopreserved time: 63 days). The procedure involved lifting the corneal flap, implanting the lenticule, and repositioning the flap. Over a follow-up period of at least one year, uncorrected distance visual acuity (UDVA) improved from 1.52 ± 0.40 preoperatively to 0.74 ± 0.28 LogMAR. Two eyes gained one line of corrected distance visual acuity (CDVA), three gained two lines, and one gained over three lines. Spherical equivalents decreased from -14.67 ± 2.36 D to -8.75 ± 4.03 D (p = 0.02). Mean anterior K and total corneal refractive power decreased (p < 0.05). Thinnest corneal thickness increased from 359.2 ± 39.3 µm to 401.7 ± 53.4 µm (p = 0.02). These findings support the potential of cryopreserved lenticules for treating post-LASIK ectasia, though further refinement in refractive predictability is needed.

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The striatum, the main input nucleus of the basal ganglia, receives topographically organized input from the cortex and gives rise to the direct and indirect output pathways, which have antagonistic effects on basal ganglia output directed to the cortex. We optogenetically stimulated the direct and indirect pathways in a visual and a working memory task in mice that responded by licking. Unilateral direct pathway stimulation increased the probability of lick responses toward the contralateral, non-stimulated side and increased cortical activity globally. In contrast, indirect pathway stimulation increased the probability of responses toward the stimulated side and decreased activity in the stimulated hemisphere. Moreover, direct pathway stimulation enhanced the neural representation of a contralateral visual stimulus during the delay of the working memory task, whereas indirect pathway stimulation had the opposite effect. Our results demonstrate how these two pathways influence perceptual decisions and working memory and modify activity in the dorsal cortex.

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Utilizing popular press books can increase accessibility and aid in retention of marginalized groups; by increasing student engagement, improving material accessibility through real-world examples, and helping ease the financial burden of textbooks. The current article outlines how several popular press books have been successfully implemented in different levels of neuroscience coursework, including an introductory neuroscience course, a mid-level drugs and behavior course, and a senior seminar. Implementation strategies and pitfalls are discussed, including best practices for assessment and incorporation of popular press books into course material.

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In July of 2023, the Faculty for Undergraduate Neuroscience (FUN) held a Summer Workshop at Western Washington University. This workshop was the first in-person workshop since 2017. This article provides a brief account of the Workshop themes of inclusive pedagogy, student and faculty mindsets, integrative STEM, and decolonization of neuroscience. The presentations and events that took place were attended by a vibrant community of close to 100, who engaged fully in the discussions and social opportunities. In addition, we review the workshop planning process to guide future FUN Summer Workshop committees and hosts.

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During the pandemic, we filmed our neuroscience labs, and now the videos provide a great resource to flip the lab. Our lab, however, covers a wide range of complicated topics, ranging from gross anatomy, immunohistochemistry (IHC) staining, and fluorescence imaging to cockroach microscopic surgery and measuring nerve conduction velocity on worms and human subjects, and it is challenging to get students to finish watching these complicated experiments. The biggest challenge that students face while watching these experiment demonstrations is their own emotions. When we were editing the films of the labs, we did not reduce the complexity, but we explained concepts by using concepts and objects that students are already familiar with so we do not trigger anxiety. To reduce boredom, we employed three major methods: questioning, humor, and increasing the pace. To address potential anxiety or reluctance about the in-person part of the lab, we mention at the beginning of every lab session that making mistakes is completely acceptable and, as they make mistakes, we help them understand what went wrong and how to correct it. We also introduce additional activities in some lab sessions to pique their interest. For instance, we ask students to test the effects of Red Bull on crickets and investigate whether students who play more video games have higher conduction velocities in the median nerve. Thus far, our flipped lab has been quite successful in terms of maintaining video retention rates and in-person attendance rates. A notable example of the effectiveness of improved hands-on skills is the cockroach microscopic surgery. Before implementing the flipped lab, only 10% of students were able to successfully complete the surgery and acquire nerve activity recordings. With the flipped lab, 90% of students were able to obtain a recording independently.

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Core concepts, or overarching principles that identify patterns in processes and phenomena, provide a framework for organizing facts and understanding. Core concepts have existed for many years in some life science disciplines, including biology, microbiology, and physiology, yet have only recently been published for neuroscience through a multi-year community-derived project which identified the following neuroscience core concepts: Communication Modalities, Emergence, Evolution, Gene-Environment Interactions, Information Processing, Nervous System Functions, Plasticity, and Structure-Function Relationship. The current phase of the core concepts work involves two arms: utilizing and "unpacking." Work on utilization of core concepts focuses on strategies for utilizing the core concepts in courses, curricula, and assessment, and in diverse institutional contexts. The process of unpacking involves deconstructing a core concept into its key underlying components. Prior to the 2023 FUN Workshop, we consulted faculty members with relevant experience to aid in the preliminary unpacking of four core concepts (Evolution, Gene-Environment Interactions, Plasticity, and Structure-Function Relationship). The preliminary drafts of the unpacked core concepts were shared at the Faculty for Undergraduate Neuroscience (FUN) Workshop and Neuroscience Teaching Conference (NTC) for community feedback and guidance. This editorial describes community feedback and guidance that we received from the conferences to inform future steps.

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Electrophysiology is one of the most intimidating topics within the foundational neuroscience curriculum to most undergraduate students. Keeping student attention and engagement during these lectures is equally challenging for educators. Game-based learning is used in many disciplines and levels of education and allows students to apply what they have learned and build community within the classroom. You're Getting on my Nerves was created to help students apply their knowledge of cable properties and practice vocabulary terms with their peers. This board game was originally created using inexpensive products but is also now available for purchase, allowing educators the flexibility to use the game within their budget and available timeframe. Additionally, it can be scaled from introductory to advanced levels and act as a relaxed and entertaining study tool. Students learn what changes in the cell can increase or decrease the action potential's ability to propagate down the axon and begin to describe different cable properties. Each player receives a card to keep track of the amplitude of their action potential. The goal is to move their game piece from the axon hillock to the axon terminal without decaying their action potential to 0. Players draw game cards that instruct them on where to move along the gameboard. The gameboard has color-coded spaces with changes in the axon. Students begin to quickly learn which changes in the cell allow their game piece to propagate forward as they compete with their peers to reach the axon terminal.

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Background: Posttraumatic stress disorder and medically unexplained pain frequently co-occur. While pain is common during traumatic events, the processing of pain during trauma and its relation to audiovisual and pain intrusions is poorly understood.Objective: Here we investigate neural activations during painful analogue trauma, focusing on areas that have been related to threat and pain processing, and how they predict intrusion formation. We also examine the moderating role of cumulative lifetime adversity.Methods: Sixty-five healthy women were assessed using functional magnetic resonance imaging. An analogue trauma was induced by an adaptation of the trauma-film paradigm extended by painful electrical stimulation in a 2 (film: aversive, neutral) x 2 (pain: pain, no-pain) design, followed by 7-day audiovisual and pain intrusion assessment using event-based ecological momentary assessment. Intrusions were fitted with Bayesian multilevel regression and a hurdle lognormal distribution.Results: Conjunction analysis confirmed a wide network including anterior insula (AI) and dorsal anterior cingulate cortex (dACC) being active both, during aversive films and pain. Pain resulted in activation in areas amongst posterior insula and deactivation in a network around ventromedial prefrontal cortex (VMPFC). Higher AI and dACC activity during aversive>neutral film predicted greater audiovisual intrusion probability over time and predicted greater audiovisual intrusion frequency particularly for participants with high lifetime adversity. Lower AI, dACC, hippocampus, and VMPFC activity during pain>no-pain predicted greater pain intrusion probability particularly for participants with high lifetime adversity. Weak regulatory VMPFC activation was associated with both increased audiovisual and pain intrusion frequency.Conclusions: Enhanced AI and dACC processing during aversive films, poor pain vs. no-pain discrimination in AI and dACC, as well as weak regulatory VMPFC processing may be driving factors for intrusion formation, particularly in combination with high lifetime adversity. Results shed light on a potential path for the etiology of PTSD and medically unexplained pain.

AI and dACC play a common role for both trauma- and pain-processing.In combination with high lifetime adversity, higher AI and dACC aversive film processing was associated with higher audiovisual intrusion frequency, whereas weaker AI and dACC pain discrimination enhanced the chance for pain intrusions.Weak regulatory VMPFC activity in aversive situations increased both audiovisual and pain intrusion formation.

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Autism spectrum disorder (ASD) affects social interaction and communication. Emerging evidence links ASD to gut microbiome alterations, suggesting that microbial composition may play a role in the disorder. This study employs explainable artificial intelligence (XAI) to examine the contributions of individual microbial species to ASD. By using local explanation embeddings and unsupervised clustering, the research identifies distinct ASD subgroups, underscoring the disorder's heterogeneity. Specific microbial biomarkers associated with ASD are revealed, and the best classifiers achieved an AU-ROC of 0.965 ± 0.005 and an AU-PRC of 0.967 ± 0.008. The findings support the notion that gut microbiome composition varies significantly among individuals with ASD. This work's broader significance lies in its potential to inform personalized interventions, enhancing precision in ASD management and classification. These insights highlight the importance of individualized microbiome profiles for developing tailored therapeutic strategies for ASD.

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Most central neurons have intricately branched dendritic trees that integrate massive numbers of synaptic inputs. Intrinsic active mechanisms in dendrites can be heterogeneous and be modulated in a branch-specific way. However, it remains poorly understood how heterogeneous intrinsic properties contribute to processing of synaptic input. We propose the first computational model of the cerebellar Purkinje cell with dendritic heterogeneity, in which each branch is an individual unit and is characterized by its own set of ion channel conductance densities. When simultaneously activating a cluster of parallel fiber synapses, we measure the peak amplitude of a response and observe how changes in P-type calcium channel conductance density shift the dendritic responses from a linear one to a bimodal one including dendritic calcium spikes and vice-versa. These changes relate to the morphology of each branch. We show how dendritic calcium spikes propagate and how Kv4.3 channels block spreading depolarization to nearby branches.

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Michel Jouvet (1925-2017) is one of the most important figures in the contemporary history of the neuroscience of sleep and dreams, and one of the most awarded French researchers of the last century. Yet this former CNRS gold medalist and winner of the Cino Del Duca World Prize remains little known-not to say unknown-outside the field of sleep medicine, especially in non-French-speaking countries, where the name of his American counterpart, William C. Dement, is more familiar. Often reduced to his experiments on cats and the discovery of what he called "paradoxical sleep," Jouvet left behind a rather unique body of work that includes not only countless publications on sleep and dreams-neurophysiological as well as ethnological and psychological-but also major contributions to clinical medicine, two novels and an impressive collection of personal dream accounts and drawings, which now make it possible to explore the nocturnal side of the last 50 years of his life. This article draws on unpublished archives to illuminate all these little-known and unknown aspects of Jouvet's life and work, highlighting his hidden links with 19th-century scientific oneirology and bringing to light its paradoxes.

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The substantia nigra pars reticulata (SNpr), an output structure of the basal ganglia, is hypothesized to gate movement execution. Previous studies in the eye movement system focusing mostly on saccades have reported that SNpr neurons are tonically active and either pause or increase their firing during movements, consistent with the gating role. We recorded activity in the SNpr of two monkeys during smooth pursuit and saccadic eye movements. SNpr neurons exhibited highly diverse reaction patterns during pursuit, including frequent increases and decreases in firing rate, uncorrelated responses in different movement directions and in reward conditions that resulted in the high dimensional activity of single neurons. These diverse temporal patterns surpassed those in other oculomotor areas in the medial-temporal cortex, frontal cortex, basal ganglia, and cerebellum. These findings suggest that temporal properties of the responses enrich the coding capacity of the basal ganglia output beyond gating or permitting movement.