Pub Date : 2024-06-08DOI: 10.1016/j.conb.2024.102884
Stefanie Geisler
Peripheral neuropathy is a common neurodegenerative condition characterized by numbness, tingling, pain, and weakness that frequently starts in the distal limbs. Arising from multiple etiologies, many peripheral neuropathies exhibit a slowly progressive course due to axon degeneration for which no effective treatments exist. During the past decade, numerous crucial insights into mechanisms of axon degeneration in peripheral neuropathies emerged from experiments involving nerve-cutting procedures, revealing the central role of the SARM1 axon degeneration pathway in both. Here I review commonalities and differences in the role of SARM1 after nerve cut and in several acquired and inherited peripheral neuropathies. This new knowledge now paves the way for the development of therapeutics that directly address root causes of various kinds of neuropathies.
{"title":"Augustus Waller’s foresight realized: SARM1 in peripheral neuropathies","authors":"Stefanie Geisler","doi":"10.1016/j.conb.2024.102884","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102884","url":null,"abstract":"<div><p>Peripheral neuropathy is a common neurodegenerative condition characterized by numbness, tingling, pain, and weakness that frequently starts in the distal limbs. Arising from multiple etiologies, many peripheral neuropathies exhibit a slowly progressive course due to axon degeneration for which no effective treatments exist. During the past decade, numerous crucial insights into mechanisms of axon degeneration in peripheral neuropathies emerged from experiments involving nerve-cutting procedures, revealing the central role of the SARM1 axon degeneration pathway in both. Here I review commonalities and differences in the role of SARM1 after nerve cut and in several acquired and inherited peripheral neuropathies. This new knowledge now paves the way for the development of therapeutics that directly address root causes of various kinds of neuropathies.</p></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"87 ","pages":"Article 102884"},"PeriodicalIF":5.7,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141291445","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}
Pub Date : 2024-06-01DOI: 10.1016/j.conb.2024.102866
Jo-Hsien Yu , Julia L. Napoli , Matthew Lovett-Barron
A variety of organisms exhibit collective movement, including schooling fish and flocking birds, where coordinated behavior emerges from the interactions between group members. Despite the prevalence of collective movement in nature, little is known about the neural mechanisms producing each individual's behavior within the group. Here we discuss how a neurobiological approach can enrich our understanding of collective behavior by determining the mechanisms by which individuals interact. We provide examples of sensory systems for social communication during collective movement, highlight recent discoveries about neural systems for detecting the position and actions of social partners, and discuss opportunities for future research. Understanding the neurobiology of collective behavior can provide insight into how nervous systems function in a dynamic social world.
{"title":"Understanding collective behavior through neurobiology","authors":"Jo-Hsien Yu , Julia L. Napoli , Matthew Lovett-Barron","doi":"10.1016/j.conb.2024.102866","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102866","url":null,"abstract":"<div><p>A variety of organisms exhibit collective movement, including schooling fish and flocking birds, where coordinated behavior emerges from the interactions between group members. Despite the prevalence of collective movement in nature, little is known about the neural mechanisms producing each individual's behavior within the group. Here we discuss how a neurobiological approach can enrich our understanding of collective behavior by determining the mechanisms by which individuals interact. We provide examples of sensory systems for social communication during collective movement, highlight recent discoveries about neural systems for detecting the position and actions of social partners, and discuss opportunities for future research. Understanding the neurobiology of collective behavior can provide insight into how nervous systems function in a dynamic social world.</p></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"86 ","pages":"Article 102866"},"PeriodicalIF":5.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S095943882400028X/pdfft?md5=0f6caad4a9ad2dbddd391a1ae1487349&pid=1-s2.0-S095943882400028X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141286119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-29DOI: 10.1016/j.conb.2024.102883
Gessynger Morais-Silva , Mary Kay Lobo
The ventral pallidum is a prominent structure within the basal ganglia, regulating reward and motivational processes. Positioned at the interface between motor and limbic structures, its function is crucial to the development and maintenance of substance use disorders. Chronic drug use induces neuroplastic events in this structure, leading to long-term changes in VP neuronal activity and synaptic communication. Moreover, different neuronal populations within the VP drive drug-seeking behavior in opposite directions. This review explores the role of the VP as a hub for reward, motivation, and aversion, establishing it as an important contributor to the pathophysiology of substance use disorders.
{"title":"Refining the circuits of drug addiction: The ventral pallidum","authors":"Gessynger Morais-Silva , Mary Kay Lobo","doi":"10.1016/j.conb.2024.102883","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102883","url":null,"abstract":"<div><p>The ventral pallidum is a prominent structure within the basal ganglia, regulating reward and motivational processes. Positioned at the interface between motor and limbic structures, its function is crucial to the development and maintenance of substance use disorders. Chronic drug use induces neuroplastic events in this structure, leading to long-term changes in VP neuronal activity and synaptic communication. Moreover, different neuronal populations within the VP drive drug-seeking behavior in opposite directions. This review explores the role of the VP as a hub for reward, motivation, and aversion, establishing it as an important contributor to the pathophysiology of substance use disorders.</p></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"86 ","pages":"Article 102883"},"PeriodicalIF":5.7,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141164208","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}
Pub Date : 2024-05-04DOI: 10.1016/j.conb.2024.102882
Rolf J. Skyberg, Cristopher M. Niell
In the natural world, animals use vision for a wide variety of behaviors not reflected in most laboratory paradigms. Although mice have low-acuity vision, they use their vision for many natural behaviors, including predator avoidance, prey capture, and navigation. They also perform active sensing, moving their head and eyes to achieve behavioral goals and acquire visual information. These aspects of natural vision result in visual inputs and corresponding behavioral outputs that are outside the range of conventional vision studies but are essential aspects of visual function. Here, we review recent studies in mice that have tapped into natural behavior and active sensing to reveal the computational logic of neural circuits for vision.
{"title":"Natural visual behavior and active sensing in the mouse","authors":"Rolf J. Skyberg, Cristopher M. Niell","doi":"10.1016/j.conb.2024.102882","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102882","url":null,"abstract":"<div><p>In the natural world, animals use vision for a wide variety of behaviors not reflected in most laboratory paradigms. Although mice have low-acuity vision, they use their vision for many natural behaviors, including predator avoidance, prey capture, and navigation. They also perform active sensing, moving their head and eyes to achieve behavioral goals and acquire visual information. These aspects of natural vision result in visual inputs and corresponding behavioral outputs that are outside the range of conventional vision studies but are essential aspects of visual function. Here, we review recent studies in mice that have tapped into natural behavior and active sensing to reveal the computational logic of neural circuits for vision.</p></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"86 ","pages":"Article 102882"},"PeriodicalIF":5.7,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959438824000448/pdfft?md5=611298141ac3c3e31994532868c4200e&pid=1-s2.0-S0959438824000448-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although aggression is associated with several psychiatric disorders, there is no effective treatment nor a rigorous definition for “pathological aggression”. Mice make a valuable model for studying aggression. They have a dynamic social structure that depends on the habitat and includes reciprocal interactions between the mice's aggression levels, social dominance hierarchy (SDH), and resource allocation. Nevertheless, the classical behavioral tests for territorial aggression and SDH in mice are reductive and have limited ethological and translational relevance. Recent work has explored the use of semi-natural environments to simultaneously study dominance-related behaviors, resource allocation, and aggressive behavior. Semi-natural setups allow experimental control of the environment combined with manipulations of neural activity. We argue that these setups can help bridge the translational gap in aggression research toward discovering neuronal mechanisms underlying maladaptive aggression.
{"title":"Studying dominance and aggression requires ethologically relevant paradigms","authors":"Yair Shemesh , Asaf Benjamin , Keren Shoshani-Haye , Ofer Yizhar , Alon Chen","doi":"10.1016/j.conb.2024.102879","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102879","url":null,"abstract":"<div><p>Although aggression is associated with several psychiatric disorders, there is no effective treatment nor a rigorous definition for “pathological aggression”. Mice make a valuable model for studying aggression. They have a dynamic social structure that depends on the habitat and includes reciprocal interactions between the mice's aggression levels, social dominance hierarchy (SDH), and resource allocation. Nevertheless, the classical behavioral tests for territorial aggression and SDH in mice are reductive and have limited ethological and translational relevance. Recent work has explored the use of semi-natural environments to simultaneously study dominance-related behaviors, resource allocation, and aggressive behavior. Semi-natural setups allow experimental control of the environment combined with manipulations of neural activity. We argue that these setups can help bridge the translational gap in aggression research toward discovering neuronal mechanisms underlying maladaptive aggression.</p></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"86 ","pages":"Article 102879"},"PeriodicalIF":5.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140815294","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}
Pub Date : 2024-05-01DOI: 10.1016/j.conb.2024.102881
Ilya E. Monosov , Jan Zimmermann , Michael J. Frank , Mackenzie W. Mathis , Justin T. Baker
Studying the intricacies of individual subjects' moods and cognitive processing over extended periods of time presents a formidable challenge in medicine. While much of systems neuroscience appropriately focuses on the link between neural circuit functions and well-constrained behaviors over short timescales (e.g., trials, hours), many mental health conditions involve complex interactions of mood and cognition that are non-stationary across behavioral contexts and evolve over extended timescales. Here, we discuss opportunities, challenges, and possible future directions in computational psychiatry to quantify non-stationary continuously monitored behaviors. We suggest that this exploratory effort may contribute to a more precision-based approach to treating mental disorders and facilitate a more robust reverse translation across animal species. We conclude with ethical considerations for any field that aims to bridge artificial intelligence and patient monitoring.
{"title":"Ethological computational psychiatry: Challenges and opportunities","authors":"Ilya E. Monosov , Jan Zimmermann , Michael J. Frank , Mackenzie W. Mathis , Justin T. Baker","doi":"10.1016/j.conb.2024.102881","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102881","url":null,"abstract":"<div><p>Studying the intricacies of individual subjects' moods and cognitive processing over extended periods of time presents a formidable challenge in medicine. While much of systems neuroscience appropriately focuses on the link between neural circuit functions and well-constrained behaviors over short timescales (e.g., trials, hours), many mental health conditions involve complex interactions of mood and cognition that are non-stationary across behavioral contexts and evolve over extended timescales. Here, we discuss opportunities, challenges, and possible future directions in computational psychiatry to quantify non-stationary continuously monitored behaviors. We suggest that this exploratory effort may contribute to a more precision-based approach to treating mental disorders and facilitate a more robust reverse translation across animal species. We conclude with ethical considerations for any field that aims to bridge artificial intelligence and patient monitoring.</p></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"86 ","pages":"Article 102881"},"PeriodicalIF":5.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959438824000436/pdfft?md5=a2eb6d49737b21040cee71b744fcfddc&pid=1-s2.0-S0959438824000436-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140815555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24DOI: 10.1016/j.conb.2024.102878
Anna Vanessa Stempel
Instinctive behaviours have evolved across animal phyla and ensure the survival of both the individual and species. They include behaviours that achieve defence, feeding, aggression, sexual reproduction, or parental care. Within the vertebrate subphylum, the brain circuits that support instinctive behaviour output are evolutionarily conserved, being present in the oldest group of living vertebrates, the lamprey. Here, I will provide an evolutionary and comparative perspective on the function of a conserved brainstem region central to the initiation and execution of virtually all instinctive behaviours—the periaqueductal gray. In particular, I will focus on recent advances on the neural mechanisms in the periaqueductal gray that underlie the production of different instinctive behaviours within and across species.
{"title":"A conserved brainstem region for instinctive behaviour control: The vertebrate periaqueductal gray","authors":"Anna Vanessa Stempel","doi":"10.1016/j.conb.2024.102878","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102878","url":null,"abstract":"<div><p>Instinctive behaviours have evolved across animal phyla and ensure the survival of both the individual and species. They include behaviours that achieve defence, feeding, aggression, sexual reproduction, or parental care. Within the vertebrate subphylum, the brain circuits that support instinctive behaviour output are evolutionarily conserved, being present in the oldest group of living vertebrates, the lamprey. Here, I will provide an evolutionary and comparative perspective on the function of a conserved brainstem region central to the initiation and execution of virtually all instinctive behaviours—the periaqueductal gray. In particular, I will focus on recent advances on the neural mechanisms in the periaqueductal gray that underlie the production of different instinctive behaviours within and across species.</p></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"86 ","pages":"Article 102878"},"PeriodicalIF":5.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959438824000400/pdfft?md5=032019d6364dea92661d13c1837202ed&pid=1-s2.0-S0959438824000400-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-23DOI: 10.1016/j.conb.2024.102880
Runita N. Shirdhankar , E. Pascal Malkemper
Navigation requires a network of neurons processing inputs from internally generated cues and external landmarks. Most studies on the neuronal basis of navigation in vertebrates have focused on rats and mice and the canonical senses vision, hearing, olfaction, and somatosensation. Some animals have evolved the ability to sense the Earth's magnetic field and use it for orientation. It can be expected that in these animals magnetic cues are integrated with other sensory cues in the cognitive map. We provide an overview of the behavioral evidence and brain regions involved in magnetic sensing in support of this idea, hoping that this will guide future experiments.
{"title":"Cognitive maps and the magnetic sense in vertebrates","authors":"Runita N. Shirdhankar , E. Pascal Malkemper","doi":"10.1016/j.conb.2024.102880","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102880","url":null,"abstract":"<div><p>Navigation requires a network of neurons processing inputs from internally generated cues and external landmarks. Most studies on the neuronal basis of navigation in vertebrates have focused on rats and mice and the canonical senses vision, hearing, olfaction, and somatosensation. Some animals have evolved the ability to sense the Earth's magnetic field and use it for orientation. It can be expected that in these animals magnetic cues are integrated with other sensory cues in the cognitive map. We provide an overview of the behavioral evidence and brain regions involved in magnetic sensing in support of this idea, hoping that this will guide future experiments.</p></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"86 ","pages":"Article 102880"},"PeriodicalIF":5.7,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959438824000424/pdfft?md5=0a0b09864f8bf7dc49cc342ea6d6e206&pid=1-s2.0-S0959438824000424-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140640983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-22DOI: 10.1016/j.conb.2024.102876
Erica N. Shook , George Thomas Barlow , Daniella Garcia-Rosales , Connor J. Gibbons , Tessa G. Montague
The coleoid cephalopods (cuttlefish, octopus, and squid) are a group of soft-bodied mollusks that exhibit a wealth of complex behaviors, including dynamic camouflage, object mimicry, skin-based visual communication, and dynamic body patterns during sleep. Many of these behaviors are visually driven and engage the animals’ color changing skin, a pixelated display that is directly controlled by neurons projecting from the brain. Thus, cephalopod skin provides a direct readout of neural activity in the brain. During camouflage, cephalopods recreate on their skin an approximation of what they see, providing a window into perceptual processes in the brain. Additionally, cephalopods communicate their internal state during social encounters using innate skin patterns, and create waves of pigmentation on their skin during periods of arousal. Thus, by leveraging the visual displays of cephalopods, we can gain insight into how the external world is represented in the brain and how this representation is transformed into a recapitulation of the world on the skin. Here, we describe the rich skin behaviors of the coleoid cephalopods, what is known about cephalopod neuroanatomy, and how advancements in gene editing, machine learning, optical imaging, and electrophysiological tools may provide an opportunity to explore the neural bases of these fascinating behaviors.
{"title":"Dynamic skin behaviors in cephalopods","authors":"Erica N. Shook , George Thomas Barlow , Daniella Garcia-Rosales , Connor J. Gibbons , Tessa G. Montague","doi":"10.1016/j.conb.2024.102876","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102876","url":null,"abstract":"<div><p>The coleoid cephalopods (cuttlefish, octopus, and squid) are a group of soft-bodied mollusks that exhibit a wealth of complex behaviors, including dynamic camouflage, object mimicry, skin-based visual communication, and dynamic body patterns during sleep. Many of these behaviors are visually driven and engage the animals’ color changing skin, a pixelated display that is directly controlled by neurons projecting from the brain. Thus, cephalopod skin provides a direct readout of neural activity in the brain. During camouflage, cephalopods recreate on their skin an approximation of what they see, providing a window into perceptual processes in the brain. Additionally, cephalopods communicate their internal state during social encounters using innate skin patterns, and create waves of pigmentation on their skin during periods of arousal. Thus, by leveraging the visual displays of cephalopods, we can gain insight into how the external world is represented in the brain and how this representation is transformed into a recapitulation of the world on the skin. Here, we describe the rich skin behaviors of the coleoid cephalopods, what is known about cephalopod neuroanatomy, and how advancements in gene editing, machine learning, optical imaging, and electrophysiological tools may provide an opportunity to explore the neural bases of these fascinating behaviors.</p></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"86 ","pages":"Article 102876"},"PeriodicalIF":5.7,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959438824000382/pdfft?md5=a36f669047da30adaeffdfaf12591cfd&pid=1-s2.0-S0959438824000382-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-16DOI: 10.1016/j.conb.2024.102877
Rebecca M. Beiter , Patrick W. Sheehan , Dorothy P. Schafer
Microglia are tissue-resident macrophages and professional phagocytes of the central nervous system (CNS). In development, microglia-mediated phagocytosis is important for sculpting the cellular architecture. This includes the engulfment of dead/dying cells, pruning extranumerary synapses and axons, and phagocytosing fragments of myelin sheaths. Intriguingly, these developmental phagocytic mechanisms by which microglia sculpt the CNS are now appreciated as important for eliminating synapses, myelin, and proteins during neurodegeneration. Here, we discuss parallels between neurodevelopment and neurodegeneration, which highlights how development is informing disease. We further discuss recent advances and challenges towards therapeutically targeting these phagocytic pathways and how we can leverage development to overcome these challenges.
{"title":"Microglia phagocytic mechanisms: Development informing disease","authors":"Rebecca M. Beiter , Patrick W. Sheehan , Dorothy P. Schafer","doi":"10.1016/j.conb.2024.102877","DOIUrl":"https://doi.org/10.1016/j.conb.2024.102877","url":null,"abstract":"<div><p>Microglia are tissue-resident macrophages and professional phagocytes of the central nervous system (CNS). In development, microglia-mediated phagocytosis is important for sculpting the cellular architecture. This includes the engulfment of dead/dying cells, pruning extranumerary synapses and axons, and phagocytosing fragments of myelin sheaths. Intriguingly, these developmental phagocytic mechanisms by which microglia sculpt the CNS are now appreciated as important for eliminating synapses, myelin, and proteins during neurodegeneration. Here, we discuss parallels between neurodevelopment and neurodegeneration, which highlights how development is informing disease. We further discuss recent advances and challenges towards therapeutically targeting these phagocytic pathways and how we can leverage development to overcome these challenges.</p></div>","PeriodicalId":10999,"journal":{"name":"Current Opinion in Neurobiology","volume":"86 ","pages":"Article 102877"},"PeriodicalIF":5.7,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140557394","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}