{"title":"The sympathetic neurons in the gut: Perspectives on metabolic and immune health and diseases","authors":"Yongwen Wan , Chengrui Cao , Wenwen Zeng","doi":"10.1016/j.conb.2025.103051","DOIUrl":"10.1016/j.conb.2025.103051","url":null,"abstract":"<div><div><strong>Purpose of review:</strong> The sympathetic nervous system (SNS), a crucial regulator of systemic homeostasis, connects the brain and peripheral organs through complex neural circuits. Often termed the “second brain,” the gut responds to sympathetic innervation to coordinate physiological processes such as digestive motility, nutrient absorption, and immune surveillance, unveiling fundamental and potentially translational significance. Therefore, timely exploration of sympathetic-gut communication is essential. <strong>Recent findings:</strong> Previous studies have revealed that sympathetic signaling inhibits intestinal peristalsis and blood flow while enhancing nutrient assimilation during feeding. Emerging evidence further identifies a neuro-metabolic axis in which sympathetic activity suppresses enteroendocrine hormone secretion, thereby linking systemic energy balance to central nervous system function. Additionally, bidirectional SNS-immune interactions have been uncovered; these pathways govern antimicrobial defense yet paradoxically exacerbate inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and colorectal cancer (CRC). <strong>Summary:</strong> This review briefly summarizes anatomical insights into sympathetic-gut projections, highlights their dual roles in metabolic homeostasis and immune modulation, and explores therapeutic opportunities targeting sympathetic pathways for gut-related disorders.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"93 ","pages":"Article 103051"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chemogenetic and optogenetic tools revolutionizing the study of astrocytes in memory","authors":"Shay Meron Asher, Inbal Goshen","doi":"10.1016/j.conb.2025.103057","DOIUrl":"10.1016/j.conb.2025.103057","url":null,"abstract":"<div><div>Memory research has been historically centered around neurons, but the understanding that neurons do not work alone is lately gaining traction. Investigation of astrocytes provides evidence of the involvement of these glial cells throughout all memory stages and in many types of memory tests. This field is constantly developing and changing through the adoption of a variety of techniques. In this review, we will focus on recent papers that have used optogenetic and chemogenetic tools, which are time-restricted and cell-type specific, to investigate astrocytic involvement in memory. We will also discuss some new tools that are starting to be implemented in astrocyte research and how they may be used in future exploration of the link between specific astrocytic activity and memory.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"93 ","pages":"Article 103057"},"PeriodicalIF":4.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144147961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neural-circuit architecture underlying non-image-forming visual functions","authors":"Jiawei Shen , Tian Xue","doi":"10.1016/j.conb.2025.103052","DOIUrl":"10.1016/j.conb.2025.103052","url":null,"abstract":"<div><div>Perceiving and responding to environmental cues underpins survival and cognition. Light, emerging as one of the most ancient and powerful signals, has shaped life on Earth for billions of years. In mammals, light information is primarily detected by retinal photoreceptors: rods, cones, and intrinsically photosensitive retinal ganglion cells. While rods and cones enable image-forming vision, evolution has preserved and extended evolutionarily ancient yet critical non-image-forming visual functions, including circadian photoentrainment, pupillary light reflexes, and light-mediated modulation of metabolism, mood, and neurodevelopment. Although non-image-forming visual functions have been partially characterized in humans and model organisms, our understanding of the neural circuit mechanisms by which light orchestrates diverse behavior remains fragmented. The discovery of ipRGCs, combined with recent advances in systems neuroscience tools, has yielded critical breakthroughs in three domains: (1) light information encoding within photoreceptors, (2) systematic mapping of retinofugal pathways, and (3) central mechanisms of light-regulated physiological functions. These advances have progressively unraveled causal relationships between non-image-forming visual functions and their underlying eye-brain circuitry. This review summarizes groundbreaking progress in the three domains discussed above, highlighting key unresolved questions in the field.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"93 ","pages":"Article 103052"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erin Wosnitzka, Lisa Gambarotto, Vassiliki Nikoletopoulou
{"title":"Macroautophagy at the service of synapses","authors":"Erin Wosnitzka, Lisa Gambarotto, Vassiliki Nikoletopoulou","doi":"10.1016/j.conb.2025.103054","DOIUrl":"10.1016/j.conb.2025.103054","url":null,"abstract":"<div><div>Post-mitotic and highly polarized neurons are dependent on the fitness of their synapses, which are often found a long distance away from the soma. How the synaptic proteome is maintained, dynamically reshaped, and continuously turned over is a topic of intense investigation. Autophagy, a highly conserved, lysosome-mediated degradation pathway has emerged as a vital component of long-term neuronal maintenance, and now more specifically of synaptic homeostasis. Here, we review the most recent findings on how autophagy undergoes both dynamic and local regulation at the synapse, and how it contributes to pre- and post-synaptic proteostasis and function. We also discuss the insights and open questions that this new evidence brings.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"93 ","pages":"Article 103054"},"PeriodicalIF":4.8,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neuromodulatory processing in the bi-pathway brain architecture","authors":"Fu-Ning Li , Chang-Mei Zhang , Jiu-Lin Du","doi":"10.1016/j.conb.2025.103055","DOIUrl":"10.1016/j.conb.2025.103055","url":null,"abstract":"<div><div>The brain is inherently a complex and parallel system that processes both external and internal sensory cues to generate adaptive responses. Sensory cues encapsulate not only objective information about their physical and chemical properties but also subjective information related to their ecological significance. Objective information is processed and conveyed through relatively stereotyped sensorimotor pathways to drive behaviors, while subjective information is received and transmitted through relatively flexible neuromodulatory systems. These neuromodulatory pathways influence signal processing of the sensorimotor pathways at multiple stages by modulating neuronal excitability and the efficiency of synaptic transmission, thereby endowing animals with flexibility. This sophisticated neuromodulatory processing is finely tuned by the spatiotemporal dynamics of various neuromodulators released from specialized neuromodulatory neurons that encode sensory, motor as well as cognitive variables. Dysfunctions in neuromodulatory pathways disrupt spatiotemporal patterns of neuromodulators, which in turn compromise sensorimotor transformation and cognitive functions. This review aims to delineate the mechanisms and roles of neuromodulatory processing within the bi-pathway brain architecture and propose prospective research topics along with innovative experimental paradigms.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"93 ","pages":"Article 103055"},"PeriodicalIF":4.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Noncoding RNA gives agency to the molecular and cellular substrates of learning and memory","authors":"Alexander D. Walsh , Timothy W. Bredy","doi":"10.1016/j.conb.2025.103044","DOIUrl":"10.1016/j.conb.2025.103044","url":null,"abstract":"<div><div>In the past decade, there has been a virtual explosion in the appreciation and study of noncoding RNA (ncRNA) in the brain. Rapidly emerging evidence suggests that many classes of ncRNA coordinate processes related to learning and memory, achieved via their precise subcellular localisation and interactions with DNA, mRNA and RNA binding proteins. Here we discuss these mechanisms using examples of recently discovered and well-studied ncRNAs, including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs), which are directly involved in regulating experience-dependent neural plasticity.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"93 ","pages":"Article 103044"},"PeriodicalIF":4.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Accessing the viscera: Technologies for interoception research","authors":"Karen K.L. Pang , Rajib Mondal , Atharva Sahasrabudhe , Polina Anikeeva","doi":"10.1016/j.conb.2025.103050","DOIUrl":"10.1016/j.conb.2025.103050","url":null,"abstract":"<div><div>Interoception, or the perception and regulation of body signals by the central nervous system, is critical for maintaining homeostasis and coordination of behaviors. Deciphering the mechanisms of interoception requires identifying pathways and decoding of diverse signals across the brain-body axis. These studies are enabled by tools to modulate and record physiological processes in the brain and visceral organs. While numerous advanced neurotechnologies are well-established in the brain, these techniques often offer limited utility for other organs, such as the gastrointestinal tract, heart, liver, or bladder. In this review, we highlight recent advances in technologies for recording and modulation of visceral organ physiology in small animals <em>in vivo,</em> with a focus on implantable bioelectronic organ interfaces that can be deployed in behaving animals. We discuss how such interfaces are made possible through innovations in materials and electronics and outline unmet technological challenges in interoception research.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"93 ","pages":"Article 103050"},"PeriodicalIF":4.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabrizia Pipicelli , Ana Villalba , Simon Hippenmeyer
{"title":"How radial glia progenitor lineages generate cell-type diversity in the developing cerebral cortex","authors":"Fabrizia Pipicelli , Ana Villalba , Simon Hippenmeyer","doi":"10.1016/j.conb.2025.103046","DOIUrl":"10.1016/j.conb.2025.103046","url":null,"abstract":"<div><div>The cerebral cortex is arguably the most complex organ in humans. The cortical architecture is characterized by a remarkable diversity of neuronal and glial cell types that make up its neuronal circuits. Following a precise temporally ordered program, radial glia progenitor (RGP) cells generate all cortical excitatory projection neurons and glial cell-types. Cortical excitatory projection neurons are produced either directly or via intermediate progenitors, through indirect neurogenesis. How the extensive cortical cell-type diversity is generated during cortex development remains, however, a fundamental open question. How do RGPs quantitatively and qualitatively generate all the neocortical neurons? How does direct and indirect neurogenesis contribute to the establishment of neuronal and lineage heterogeneity? Whether RGPs represent a homogeneous and/or multipotent progenitor population, or if RGPs consist of heterogeneous groups is currently also not known. In this review, we will summarize the latest findings that contributed to a deeper insight into the above key questions.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"93 ","pages":"Article 103046"},"PeriodicalIF":4.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of moonlighting proteins in neurogenesis","authors":"Florencia Merino , Magdalena Götz","doi":"10.1016/j.conb.2025.103047","DOIUrl":"10.1016/j.conb.2025.103047","url":null,"abstract":"<div><div>The complexity of the mammalian brain must arise from a comparably small number of genes. Proteins with moonlighting functions, i.e. entirely different functions in different compartments or cell types, contribute to multiply functional diversity. Here we review examples of such proteins with moonlighting functions during neurogenesis and in neuronal maturation. These range from cytoskeletal proteins acting as transcriptional regulators or synaptic proteins or exon junction proteins binding to and regulating the cytoskeleton to immediate early gene transcription factors regulating lipid metabolism in the endoplasmic reticulum. We further discuss how proteins with such moonlighting functions contribute to the heterogeneity of organelles shaping cell-type diversity in the brain.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"93 ","pages":"Article 103047"},"PeriodicalIF":4.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular mechanisms of stimulus detection and secretion in enteroendocrine cells","authors":"Adam Davison, Frank Reimann , Fiona M. Gribble","doi":"10.1016/j.conb.2025.103045","DOIUrl":"10.1016/j.conb.2025.103045","url":null,"abstract":"<div><div>Enteroendocrine cells (EECs) secrete over 20 different gut hormones in response to changes to the gut environment. They detect a range of nutritional stimuli through activation of a host of nutrient-sensing G-protein–coupled receptors and electrogenic nutrient cotransport. These activate intracellular signalling pathways which converge on membrane depolarisation and action potential generation, which elicit secretion. Emerging evidence has demonstrated that EECs also respond to non-nutritional stimuli, including mechanosensation, pH changes, and metabolites produced by the gut microbiome. EECs are polyhormonal cells, in which hormone expression is plastic and dependent on location in the gut. Hormones and small-molecule neurotransmitters secreted by EECs can activate extrinsic vagal afferents, modulating central processes such as appetite and food preference. While neuronal afferents are sometimes found in close proximity to EECs, the extent to which EEC/neuronal connections recapitulate traditional synaptic connections remains undefined.</div></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"92 ","pages":"Article 103045"},"PeriodicalIF":4.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143947550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}