Dimitra Vardalaki, Courtney E Yaeger, Mark T Harnett
{"title":"Silent Synapses in the Adult Brain.","authors":"Dimitra Vardalaki, Courtney E Yaeger, Mark T Harnett","doi":"10.1146/annurev-neuro-112723-032924","DOIUrl":"10.1146/annurev-neuro-112723-032924","url":null,"abstract":"<p><p>The formation of new synapses, the connections between neurons, is the critical step for neural circuit assembly. Newly formed glutamatergic synapses are initially silent and require activity-dependent plasticity to become fully functional connections. While these synapses have long been considered a vital part of the developmental program for neural networks, recent findings now indicate that silent synapses are a key source of neural circuit plasticity in the adult brain. Here, we review current evidence for silent synapses in the adult brain and explore the potential roles of these highly plastic structures. We argue that silent synapses may be instrumental in adult neural circuit remodeling and can serve as a latent reservoir of plasticity that enhances information processing and storage. This previously underappreciated aspect of adult plasticity underscores the need for innovative approaches and further investigation into the dynamic contribution of silent synapses to learning and memory in the adult brain.</p>","PeriodicalId":8008,"journal":{"name":"Annual review of neuroscience","volume":" ","pages":"169-189"},"PeriodicalIF":12.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143498027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Sachkova, Vengamanaidu Modepalli, Maike Kittelmann
{"title":"The Deep Evolutionary Roots of the Nervous System.","authors":"Maria Sachkova, Vengamanaidu Modepalli, Maike Kittelmann","doi":"10.1146/annurev-neuro-112723-040945","DOIUrl":"10.1146/annurev-neuro-112723-040945","url":null,"abstract":"<p><p>The evolutionary success of animals can, at least in part, be attributed to the presence of neurons that allow long-distance communication between tissues, coordination of movements, and the capacity for learning. However, the evolutionary origin and relationship of neurons to other cell types are fundamental questions that remain unsolved. The first neurons probably evolved shortly after the rise of the first animals over 600 million years ago. Studies on early-diverging animal lineages have provided key insights into the mechanisms underlying the origin of neurons. Recent discoveries in morphology, molecular signatures, and function of neurons in cnidarians and comb jellies, as well as neuron-like cells in nerveless placozoans, sponges, and other eukaryotes, may prompt a redefinition of what constitutes a neuron. Here we review the latest insights into the origin of neurons and nervous systems, while also highlighting exciting technological advancements that not only are accelerating our understanding of nervous system evolution, morphology, and function but also hold the potential to revolutionize the field.</p>","PeriodicalId":8008,"journal":{"name":"Annual review of neuroscience","volume":" ","pages":"311-329"},"PeriodicalIF":12.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How the Hippocampal Cognitive Map Supports Flexible Navigation.","authors":"John O'Keefe","doi":"10.1146/annurev-neuro-112723-023341","DOIUrl":"10.1146/annurev-neuro-112723-023341","url":null,"abstract":"<p><p>During navigation to a goal, a portion of the hippocampal place cells exhibit directional preferences, firing more in some directions than in others. These directional preferences create vector fields oriented toward locations scattered around the environment called ConSinks. The population vector field averaged across all of the cells recorded in each animal flows toward an average ConSink located close to the goal, providing a means for navigation in unobstructed environments. Closer examination of the ConSink place cell directional firing reveals a fantail representation in which alternative paths to the goal are evaluated, providing the basis for flexible navigation. Additional assumptions about how obstructions might be represented suggest a solution for navigation in more complicated environments. Implications for the phenomena of directionality on linear tracks and splitter cells are discussed.</p>","PeriodicalId":8008,"journal":{"name":"Annual review of neuroscience","volume":" ","pages":"331-344"},"PeriodicalIF":12.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adaptive Cost-Benefit Control Fueled by Striatal Dopamine.","authors":"Michael J Frank","doi":"10.1146/annurev-neuro-112723-025228","DOIUrl":"10.1146/annurev-neuro-112723-025228","url":null,"abstract":"<p><p>The twenty-first century has brought forth a deluge of theories and data shedding light on the neural mechanisms of motivated behavior. Much of this progress has focused on dopaminergic dynamics, including their signaling properties (how do they vary with expectations and outcomes?) and their downstream impacts in target regions (how do they affect learning and behavior?). In parallel, the basal ganglia have been elevated from their original implication in motoric function to a canonical circuit facilitating the initiation, invigoration, and selection of actions across levels of abstraction, from motor to cognitive operations. This review considers how striatal D1 and D2 opponency allows animals to perform cost-benefit calculations across multiple scales: locally, whether to select a given action, and globally, whether to engage a particular corticostriatal circuit for guiding behavior. An emerging understanding of such functions reconciles seemingly conflicting data and has implications for neuroscience, psychology, behavioral economics, and artificial intelligence.</p>","PeriodicalId":8008,"journal":{"name":"Annual review of neuroscience","volume":" ","pages":"1-22"},"PeriodicalIF":12.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oluwadamilola O Lawal, Dayu Lin, Julieta E Lischinsky
{"title":"Estrogen Control of Social Behaviors.","authors":"Oluwadamilola O Lawal, Dayu Lin, Julieta E Lischinsky","doi":"10.1146/annurev-neuro-112723-041639","DOIUrl":"10.1146/annurev-neuro-112723-041639","url":null,"abstract":"<p><p>Social behaviors, including parental care, mating, and fighting, all depend on the hormonal milieu of an organism. Decades of work highlighted estrogen as a key hormonal controller of social behaviors, exerting its influence primarily through binding to estrogen receptor alpha (ERα). Recent technological advances in chemogenetics, optogenetics, gene editing, and transgenic model organisms have allowed for a detailed understanding of the neuronal subpopulations and circuits for estrogen action across <i>Esr1</i>-expressing interconnected brain regions. Focusing on rodent studies, in this review we examine classical and contemporary research demonstrating the multifaceted role of estrogen and ERα in regulating social behaviors in a sex-specific and context-dependent manner. We highlight gaps in knowledge, particularly a missing link in the molecular cascade that allows estrogen to exert such a diverse behavioral repertoire through the coordination of gene expression changes. Understanding the molecular and cellular basis of ERα's action in social behaviors provides insights into the broader mechanisms of hormone-driven behavior modulation across the lifespan.</p>","PeriodicalId":8008,"journal":{"name":"Annual review of neuroscience","volume":" ","pages":"125-147"},"PeriodicalIF":12.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phase Separation-Mediated Compartmentalization Underlies Synapse Formation and Plasticity.","authors":"Xiandeng Wu, Zeyu Shen, Mingjie Zhang","doi":"10.1146/annurev-neuro-112723-040159","DOIUrl":"10.1146/annurev-neuro-112723-040159","url":null,"abstract":"<p><p>The synapse is polarized and highly compartmentalized on both its pre- and postsynaptic sides. The compartmentalization of synaptic vesicles, as well as vesicle releasing and recycling machineries, allows neurotransmitters to be released with precisely controlled timing, speed, and amplitude. The compartmentalized and clustered organization of neurotransmitter receptors and their downstream signaling enzymes allows neuronal signals to be properly received and amplified. Synaptic adhesion molecules also form clustered assemblies to align pre- and postsynaptic subcompartments for synaptic formation, stability, and transmission. Recent studies indicate that such synaptic and subsynaptic compartmentalized organizations are formed via phase separation. This review discusses how such condensed subsynaptic compartments may form and function in the context of synapse formation and plasticity. We discuss how phase separation allows for the formation of multiple distinct condensates on both sides of a synapse and how such condensates communicate with each other. We also highlight how proteins display unique properties in condensed phases compared to the same proteins in dilute solutions.</p>","PeriodicalId":8008,"journal":{"name":"Annual review of neuroscience","volume":" ","pages":"149-168"},"PeriodicalIF":12.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Macauley Smith Breault, Sirma Orguc, Ohyoon Kwon, Gloria H Kang, Bryan Tseng, David R Schreier, Emery N Brown
{"title":"Anesthetics as Treatments for Depression: Clinical Insights and Underlying Mechanisms.","authors":"Macauley Smith Breault, Sirma Orguc, Ohyoon Kwon, Gloria H Kang, Bryan Tseng, David R Schreier, Emery N Brown","doi":"10.1146/annurev-neuro-112723-062031","DOIUrl":"10.1146/annurev-neuro-112723-062031","url":null,"abstract":"<p><p>Major depressive disorder and treatment-resistant depression are significant worldwide health problems that need new therapies. The success of the anesthetic ketamine as an antidepressant is well known. It is less widely known that several other anesthetic agents have also shown antidepressant effects. These include nitrous oxide, propofol, isoflurane, sevoflurane, dexmedetomidine, and xenon. We review clinical and basic science investigations that have studied the therapeutic value of these anesthetics for treating depression. We propose potential neurophysiological mechanisms underlying the antidepressant effects of anesthetics by combining our understanding of how anesthetics modulate brain dynamics to alter arousal states, current theories of depression pathophysiology, and findings from other depression treatment modalities.</p>","PeriodicalId":8008,"journal":{"name":"Annual review of neuroscience","volume":" ","pages":"103-124"},"PeriodicalIF":12.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell Type-Specific Studies of Human Tissue for Investigation of the Molecular Cell Biology of Late-Onset Neurodegenerative Disease.","authors":"Kert Mätlik, Christina Pressl, Nathaniel Heintz","doi":"10.1146/annurev-neuro-112723-025516","DOIUrl":"10.1146/annurev-neuro-112723-025516","url":null,"abstract":"<p><p>Decades of research into human neurodegenerative diseases have revealed important similarities as well as dissimilarities between diseases. While investigations of specific mechanistic aspects of diseases have been aided by cell and animal models, true advances in the understanding of neurodegeneration require that we deal with the daunting complexities of the human brain. In this review, we discuss novel molecular profiling methods that have been applied to human postmortem brain tissue during the last decade and highlight insights into cell type-specific molecular characteristics and disease-associated changes in both vulnerable and resilient cell types in Huntington's disease, Parkinson's disease, and Alzheimer's disease. We also illustrate how these approaches can complement human genetic analyses and studies of animal models to advance our understanding of human neurodegeneration.</p>","PeriodicalId":8008,"journal":{"name":"Annual review of neuroscience","volume":" ","pages":"277-295"},"PeriodicalIF":12.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neural Circuits Underlying Sexually Dimorphic Innate Behaviors.","authors":"Meital Oren-Suissa, Troy R Shirangi","doi":"10.1146/annurev-neuro-112723-034621","DOIUrl":"10.1146/annurev-neuro-112723-034621","url":null,"abstract":"<p><p>Sexually dimorphic instinctual behaviors that set females and males apart are found across animal clades. Recent studies in a variety of animal systems have provided deep insights into the neural circuits that guide sexually dimorphic behaviors, such as mating practices and social responses, and how sex differences in these circuits develop. Here, we discuss the neural circuits of several sexually dimorphic instinctual behaviors in rodents, flies, and worms-from mate attraction and aggression to pain perception and empathy. We highlight several salient similarities and differences between these circuits and reveal general principles that underlie the function and development of neural circuits for dimorphic behaviors.</p>","PeriodicalId":8008,"journal":{"name":"Annual review of neuroscience","volume":" ","pages":"191-210"},"PeriodicalIF":12.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Topological Neuroscience: Linking Circuits to Function.","authors":"Carina Curto, Nicole Sanderson","doi":"10.1146/annurev-neuro-112723-034315","DOIUrl":"10.1146/annurev-neuro-112723-034315","url":null,"abstract":"<p><p>We review recent developments of the use of topology in neuroscience. From grid cells and head direction cells to the geometry of olfactory space, modern applied topology methods such as persistent homology are increasingly being used to study neural circuits and perception. In addition to outlining the big picture and reviewing various applications of topological data analysis (TDA) to neuroscience, we take a deep dive into the basic homology computation to make the underlying mathematics more accessible to neuroscientists. A discussion of practical considerations and pointers to TDA software are also included.</p>","PeriodicalId":8008,"journal":{"name":"Annual review of neuroscience","volume":" ","pages":"491-518"},"PeriodicalIF":12.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}