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Third-order entropy for spatiotemporal neural network characterization

Journal of Neurophysiology 2025年第4期133卷 1234-1244页

作者： Deshpande, Sarita S. van Drongelen, Wim Medical Scientist Training Program University of Chicago Chicago IL United States Committee on Neurobiology University of Chicago Chicago IL United States Section of Pediatric Neurology University of Chicago Chicago IL United States Committee on Computational Neuroscience University of Chicago Chicago IL United States

The human brain comprises an intricate web of connections that generate complex neural networks capable of storing and processing information based on factors such as network structure, connectivity strength, and interactions. To further unravel and understand this information, we introduce third-order entropy, a new metric grounded in the Triple Correlation Uniqueness (TCU) theorem. Triple correlation, which provides a complete and unique characterization of the network, relates three nodes separated by up to two spatiotemporal lags. Based on these four lags, we evaluate third-order entropy from the spatiotemporal lag probability distribution function (PDF) of the network activity’s triple correlation. Given a spike raster, we compute triple correlation by iterating over time and space. Summing the contributions to the triple correlation over each of the spatial and temporal lag combinations generates a 4-D spatiotemporal frequency histogram, from which we estimate a PDF and compute entropy. To validate our approach, we first estimate third-order entropy from feedforward motifs in a simulated spike raster and then simulate the effects of adding increasing motif-class structure to a Poisson-modeled spike raster. Finally, we apply this methodology to spiking activity recorded from rat cortical cultures and compare our results to previously published results of pairwise entropy over time. Although first- and second-order metrics of activity (spike rate and cross-correlation) show agreement with previously published results, our TCU-based third-order entropy computation is a more complete tool for neural network characterization and reveals a greater depth of underlying network organization compared with pairwise entropy. NEW & NOTEWORTHY Here, we present third-order entropy built from triple correlation, which measures spatiotemporal interactions among up to three neurons. Per the Triple Correlation Uniqueness theorem, third-order entropy is based on a complete and un

关键词： entropy neural network characterization Triple Correlation Uniqueness theorem

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A Novel Catheter-Based Method for Denervation of Afferent Renal Nerves in Sheep

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Cardiovascular Engineering and Technology 2025年 1-10页

作者： de la Cruz-Lynch, Arthur Dailey-Krempel, Brianna Dayton, Alex Nguyen, Duc T. Tyshynsky, Roman Van Helden, Dusty Lahti, Matthew Carney, John Evans, Louise Vulchanova, Lucy Osborn, John Department of Surgery University of Minnesota MinneapolisMN55455 United States Department of Integrative Biology & Physiology University of Minnesota MinneapolisMN55455 United States Medical Scientist Training Program University of Minnesota MinneapolisMN55455 United States Department of Neuroscience University of Minnesota MinneapolisMN55455 United States Experimental Surgical Services Laboratory University of Minnesota MinneapolisMN55455 United States

Purpose: Catheter-based total renal denervation (TRDN) has recently gained FDA approval to lower blood pressure in patients with treatment-resistant hypertension. Current TRDN technologies indiscriminately destroy efferent (sympathetic) and afferent (sensory) renal nerves. However, preclinical studies suggest that the beneficial effects of TRDN may be due to ablation of afferent, rather than efferent, renal nerves. We developed a novel method for chemical ablation of afferent renal nerves by periaxonal application of capsaicin which has been employed in mouse and rat models of hypertension. In certain rodent models afferent-specific renal denervation (ARDN) has been shown to lower arterial pressure to the same degree as TRDN. The objective of the present study was to develop a catheter-based method for ARDN in a large animal model with the long-term goal of translating this treatment to humans. We tested the feasibility of using the Peregrine™ catheter infusion system, currently used to perform TRDN in humans by injection of ethanol, to perform catheter-based afferent renal denervation in sheep by periaxonal application of capsaicin. Methods: Castrated, adult, male, Friesen sheep underwent Sham RDN (saline, n = 2), TRDN (ethanol, n = 4), or ARDN (capsaicin, n = 4) with the Peregrine™ catheter before termination > 2 weeks after the procedure. Denervation of renal efferents was verified by measurement of renal cortical norepinephrine (NE) content and anti-tyrosine hydroxylase (TH) staining;denervation of renal afferents was verified with anti-calcitonin gene-related peptide (CGRP) staining. Results: There was a significant decrease in TH + and CGRP + fibers in TRDN kidneys and in CGRP + but not TH + fibers in ARDN kidneys. TRDN significantly reduced renal cortical norepinephrine (NE) content by 89% while ARDN had similar NE content to Sham RDN kidneys. Conclusions: This study establishes the feasibility of performing catheter-based afferent renal denervation in a larg

关键词： Rats

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An innate drive to save a life

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Science (New York, N.Y.) 2025年第6736期387卷 827-828页

作者： William M Sheeran Zoe R Donaldson Department of Molecular Cellular and Developmental Biology University of Colorado Boulder Boulder CO USA. Medical Scientist Training Program University of Colorado School of Medicine Aurora CO USA. Department of Psychology and Neuroscience University of Colorado Boulder Boulder CO USA.

In mice, two brain regions drive the impulse to revive an unconscious companion.

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Emerging Techniques in Spatial Multiomics: Fundamental Principles and Applications to Dermatology

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Journal of Investigative Dermatology 2025年第5期145卷 1017-1032页

作者： Jia, Bojing B. Sun, Bryan K. Lee, Ernest Y. Ren, Bing Bioinformatics and Systems Biology Graduate Program University of California San Diego La Jolla CA United States Medical Scientist Training Program University of California San Diego La Jolla CA United States Department of Dermatology University of California Irvine Irvine CA United States Department of Dermatology University of California San Francisco San Francisco CA United States Center for Epigenomics Department of Cellular & Molecular Medicine University of California San Diego La Jolla CA United States Institute of Genomic Medicine Moores Cancer Center School of Medicine University of California San Diego La Jolla CA United States

Molecular pathology, such as high-throughput genomic and proteomic profiling, identifies precise disease targets from biopsies but require tissue dissociation, losing valuable histologic and spatial context. Emerging spatial multi-omic technologies now enable multiplexed visualization of genomic, proteomic, and epigenomic targets within a single tissue slice, eliminating the need for labeling multiple adjacent slices. Although early work focused on RNA (spatial transcriptomics), spatial technologies can now concurrently capture DNA, genome accessibility, histone modifications, and proteins with spatially-resolved single-cell resolution. This review outlines the principles, advantages, limitations, and potential for spatial technologies to advance dermatologic research. By jointly profiling multiple molecular channels, spatial multiomics enables novel studies of copy number variations, clonal heterogeneity, and enhancer dysregulation, replete with spatial context, illuminating the skin's complex heterogeneity. © 2024 The Authors

关键词： Dermatopathology Digital pathology Multiomics Multiplexed imaging Spatial sequencing

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Epigenetic Control of an Auxiliary Subunit of Voltage-Gated Sodium Channels Regulates the Strength of Drug-Cue Associations and Relapse-Like Cocaine Seeking

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Biological Psychiatry 2025年

作者： Wood, Daniel J. Tsvetkov, Evgeny Comte-Walters, Susana Welsh, Colin L. Bloyd, Michelle Wood, Timothy G. Akiki, Rose Marie Anderson, Ethan M. Penrod, Rachel D. Madan, Lalima K. Ball, Lauren E. Taniguchi, Makoto Cowan, Christopher W. Department of Neuroscience Medical University of South Carolina Charleston South Carolina United States Medical Scientist Training Program Medical University of South Carolina Charleston South Carolina United States Department of Pharmacology and Immunology Medical University of South Carolina Charleston South Carolina United States

Background: Repeated use of addictive drugs produces long-lasting and prepotent drug-cue associations that increase vulnerability for relapse in individuals with a substance use disorder. Epigenetic factors, such as HDAC5 (histone deacetylase 5), play a key role in regulating the formation of drug-cue associations, but the underlying mechanisms remain unclear. Methods: We used a combination of molecular biology, cultured cells, tandem mass spectrometry, deacetylase activity measurements, co-immunoprecipitation, and molecular dynamics simulations to assess HDAC5 structure-activity relationships. In male and female Long Evans rats, we used viral-mediated expression of HDAC5 mutants in the nucleus accumbens (NAc) to test effects on cocaine intravenous self-administration and cue-reinstated cocaine seeking. We also used in silico analysis of single-nucleus RNA sequencing data, quantitative reverse transcriptase–polymerase chain reaction, viral-mediated expression of Scn4b short hairpin RNA, patch-clamp electrophysiology, and rat cocaine or sucrose SA to assess Scn4b's effects on NAc intrinsic excitability and cued reward seeking. Results: We discovered that 2 conserved cysteines located near HDAC5’s catalytic domain were required for its intrinsic deacetylase activity and that HDAC5’s deacetylase activity was required in NAc medium spiny neurons (MSNs) to limit relapse-like cue-reinstated cocaine seeking. Moreover, we found that HDAC5 limited cocaine-seeking, but not sucrose-seeking, behavior by reducing NAc MSN intrinsic excitability through the deacetylase-dependent repression of Scn4b, which codes for an auxiliary subunit of voltage-gated sodium channels. Conclusions: Our findings suggest that HDAC5’s control of NAc Scn4b expression governs the formation of cocaine-cue, but not sucrose-cue, associations through modulation of NAc MSN intrinsic excitability and drug-induced NAc plasticity mechanisms. © 2025 Society of Biological Psychiatry

关键词： Epigenetics Neuronal excitability Nucleus accumbens Reinstatement behavior Substance use disorder

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Orderly specification and precise laminar deployment of mouse cortical projection neuron types through intermediate progenitors

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Developmental Cell 2025年

作者： Huilgol, Dhananjay Levine, Jesse M. Galbavy, William Wang, Bor-Shuen Huang, Z. Josh Department of Neurobiology Duke University Medical Center Durham NC United States Department of Biomedical Engineering Duke University Durham NC United States Cold Spring Harbor Laboratory Cold Spring Harbor NY United States Program in Neuroscience and Medical Scientist Training Program Stony Brook University Stony Brook NY United States Program in Neuroscience Department of Neurobiology and Behavior Stony Brook University Stony Brook NY United States

The cerebral cortex comprises diverse types of glutamatergic projection neurons (PNs) generated from radial glial progenitors (RGs) through either direct neurogenesis (dNG) or indirect neurogenesis (iNG) via intermediate progenitors (IPs). A foundational concept in corticogenesis is the “inside-out” model, whereby successive generations of PNs sequentially migrate first to deep and then progressively to more superficial layers. However, its biological significance remains unclear, and the role of iNG in this process is unknown. Using genetic strategies linking PN birth dating to projection mapping in mice, we found that the laminar deployment of IP-derived PNs substantially deviates from a stringent inside-out rule: PNs destined to non-consecutive layers are generated at the same time, and different PN types of the same layer are generated at non-contiguous times. The overarching scheme of iNG is the sequential specification and precise laminar deployment of projection-defined PN types, which may contribute to the orderly assembly of cortical output channels and processing streams. © 2025 Elsevier Inc.

关键词： fate mapping indirect neurogenesis intermediate progenitors neocortex projection neurons

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Whole-body hyperthermia as a novel antidepressant therapy

Biomarkers in Neuropsychiatry

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Biomarkers in Neuropsychiatry 2025年 12卷 100124-100124页

作者： Gaitonde, Kevin D. Nasrallah, Henry A. Medical Scientist Training Program University of Cincinnati College of Medicine 3230 Eden Avenue Cincinnati 45267 OH United States Department of Psychiatry and Behavioral Neuroscience University of Cincinnati College of Medicine 260 Stetson Street Suite 3200 Cincinnati 45219 OH United States

First-line treatments for major depressive disorder include medication and cognitive behavioral therapy. While effective, pharmacotherapy often takes time to start demonstrating efficacy in symptomatic improvement and may be accompanied by adverse effects, indicating an ongoing need for new therapeutic approaches. A recently emerging somatic antidepressant intervention is whole-body hyperthermia, in which subjects are temporarily exposed to heat and then allowed to cool down. Recent studies employing hyperthermia-based strategies appear to show mood improvements both immediately and several weeks after the conclusion of treatment. However, published studies are often limited by their sample sizes and by their selection criteria. In this article, we review the literature on this novel approach and propose ideas regarding the possible physiological basis of this novel intervention and how it may be used in the future as adjunctive therapy with the current standard of care. © 2025 The Authors

关键词： Depression Hyperthermia Temperature Thermoregulation

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Semaphorin7A and PD-L1 cooperatively drive immunosuppression during mammary involution and breast cancer

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Cell Reports 2025年第5期44卷 115676页

作者： Elder, Alan M. Fairchild, Heather R. Kines, Kelsey T. Cozzens, Lauren M. Becks, Alexandria R. Slansky, Jill E. Anderson, Steven M. Lyons, Traci R. Division of Medical Oncology Department of Medicine School of Medicine University of Colorado Anschutz Medical Campus Aurora CO United States Cancer Biology Graduate Training Program University of Colorado Anschutz Medical Campus Aurora CO United States Medical Scientist Training Program University of Colorado Anschutz Medical Campus Aurora CO United States University of Colorado Cancer Center Aurora CO United States Department of Immunology and Microbiology School of Medicine University of Colorado Anschutz Medical Campus Aurora CO United States Young Women's Breast Cancer Translational Program University of Colorado Anschutz Medical Campus Aurora CO United States

Postpartum mammary gland remodeling after a pregnancy/lactation cycle is characterized by mechanisms of cell death and inflammation. Here, we show that SEMA7A promotes PD-L1 expression in immune cells of the mammary tissue during involution. These same phenotypes are mimicked in the microenvironment of SEMA7A-expressing tumors, which partially respond to αPD-1/αPD-L1 treatments in vivo. However, cells that remain after treatment are enriched for SEMA7A expression. Therefore, we tested a monoclonal antibody that directly targets SEMA7A-expressing tumors, in part, by reducing SEMA7A-mediated upregulation of PD-L1. In vivo, the SEMA7A monoclonal antibody reduces tumor growth and/or promotes complete regression of mouse mammary tumors, reduces some immunosuppressive phenotypes in the tumor microenvironment, and restores cytotoxic T cells, suggesting that SEMA7A may be a candidate for immune-based therapy for breast cancer patients. © 2025 The Author(s)

关键词： breast cancer CP: Cancer macrophage mammary gland involution PD-L1 semaphorin 7a tumor immunology tumor microenvironment

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Variable Presence of an Evolutionarily New Brain Structure Is Related to Trait Impulsivity

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Biological Psychiatry: Cognitive neuroscience and Neuroimaging 2025年

作者： Willbrand, Ethan H. Maboudian, Samira A. Elliott, Matthew V. Kellerman, Gabby M. Johnson, Sheri L. Weiner, Kevin S. Medical Scientist Training Program School of Medicine and Public Health University of Wisconsin-Madison Madison WI United States Helen Wills Neuroscience Institute University of California Berkeley Berkeley California United States Department of Neuroscience University of California Berkeley Berkeley California United States Department of Psychology University of California Berkeley Berkeley California United States

Background: Impulsivity is a multidimensional construct reflecting poor constraint over one's behaviors. Clinical psychology research has identified separable impulsivity dimensions that are each unique transdiagnostic indicators for psychopathology. However, despite this apparent clinical importance, the shared and unique neuroanatomical correlates of these factors remain largely unknown. Concomitantly, neuroimaging research has identified variably present human brain structures implicated in cognition and disorder: the folds (sulci) of the cerebral cortex located in the latest-developing and most evolutionarily expanded hominoid-specific association cortices. Methods: We tethered these 2 fields to test whether variability in one such structure in the anterior cingulate cortex (ACC)—the paracingulate sulcus (PCGS)—was related to individual differences in trait impulsivity. A total of 120 adult participants with internalizing or externalizing psychopathology completed a magnetic resonance imaging scan and the Three-Factor Impulsivity Index. Using precision imaging techniques, we manually identified the PCGS, when present, and acquired quantitative folding metrics (PCGS length and ACC local gyrification index). Results: Neuroanatomical-behavioral analyses revealed that participants with leftward or symmetrical PCGS patterns had greater severity of Lack of Follow Through (LFT)—which captures inattention and lack of perseverance—than those with rightward asymmetry. Neuroanatomical-functional analyses identified that the PCGS colocalized with a focal locus found in a neuroimaging meta-analysis on a feature underlying LFT. Neither quantitative folding metric related to any impulsivity dimension. Conclusions: This study advances understanding of the neuroanatomical correlates of impulsivity and establishes the notion that the topographical organization of distinct, hominoid-specific cortical expanses underlies separable impulsivity dimensions with robust, transdiagnostic

关键词： Cingulate cortex Impulsivity Neuroanatomy Neuroimaging Psychopathology Transdiagnostic

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The emerging role of microbiota derived SCFAs in neurodegenerative disorders

Brain, Behavior, & Immunity - Health

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Brain, Behavior, & Immunity - Health 2025年 46卷 101012-101012页

作者： Samuel Wachamo Alban Gaultier Department of Neuroscience University of Virginia Charlottesville VA USA Neuroscience Graduate Program University of Virginia Charlottesville VA USA Center for Brain Immunology and Glia University of Virginia Charlottesville VA USA Medical Scientist Training Program School of Medicine University of Virginia Charlottesville VA USA

The microbiota-gut-brain axis (MGBA), the bidirectional communication network between the gastrointestinal tract and the central nervous system, plays a significant role in the pathophysiology of neurodegenerative disorders. Emerging research highlights how gut microbiota dysbiosis, or an imbalance in the microbial community, is linked to the etiology and pathology of these conditions. Microbiota dysbiosis leads to changes in the production of microbial metabolites, such as short-chain fatty acids (SCFAs), which can cross the intestinal barrier and influence the brain either directly or indirectly. Understanding the mechanisms by which dysfunction in the MGBA contributes to neurodegeneration opens potential avenues for novel therapeutic strategies, including microbiota-targeted interventions. This review introduces the MGBA, discusses the role of SCFAs within the MGBA in the context of neurodegenerative disorders, and suggests future research directions.

关键词： Microbiota Microbiota-gut-brain axis (MGBA) Dysbiosis Short-chain fatty acids (SCFAs) Neurodegenerative disorders

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