Annual review of neuroscience最新文献

Schwann cells in the peripheral nervous system (PNS) are essential for the support and myelination of axons, ensuring fast and accurate communication between the central nervous system and the periphery. Schwann cells and related glia accompany innervating axons in virtually all tissues in the body, where they exhibit remarkable plasticity and the ability to modulate pathology in extraordinary, and sometimes surprising, ways. Here, we provide a brief overview of the various glial cell types in the PNS and describe the cornerstone cellular and molecular processes that enable Schwann cells to perform their canonical functions. We then dive into discussing exciting noncanonical functions of Schwann cells and related PNS glia, which include their role in organizing the PNS, in regulating synaptic activity and pain, in modulating immunity, in providing a pool of stem cells for different organs, and, finally, in influencing cancer.

When navigating through space, we must maintain a representation of our position in real time; when recalling a past episode, a memory can come back in a flash. Interestingly, the brain's spatial representation system, including the hippocampus, supports these two distinct timescale functions. How are neural representations of space used in the service of both real-world navigation and internal mnemonic processes? Recent progress has identified sequences of hippocampal place cells, evolving at multiple timescales in accordance with either navigational behaviors or internal oscillations, that underlie these functions. We review experimental findings on experience-dependent modulation of these sequential representations and consider how they link real-world navigation to time-compressed memories. We further discuss recent work suggesting the prevalence of these sequences beyond hippocampus and propose that these multiple-timescale mechanisms may represent a general algorithm for organizing cell assemblies, potentially unifying the dual roles of the spatial representation system in memory and navigation.

Organoids are 3D cell culture systems derived from human pluripotent stem cells that contain tissue resident cell types and reflect features of early tissue organization. Neural organoids are a particularly innovative scientific advance given the lack of accessibility of developing human brain tissue and intractability of neurological diseases. Neural organoids have become an invaluable approach to model features of human brain development that are not well reflected in animal models. Organoids also hold promise for the study of atypical cellular, molecular, and genetic features that underscore neurological diseases. Additionally, organoids may provide a platform for testing therapeutics in human cells and are a potential source for cell replacement approaches to brain injury or disease. Despite the promising features of organoids, their broad utility is tempered by a variety of limitations yet to be overcome, including lack of high-fidelity cell types, limited maturation, atypical physiology, and lack of arealization, features that may limit their reliability for certain applications.

Ventral tegmental area (VTA) dopamine (DA) neurons are often thought to uniformly encode reward prediction errors. Conversely, DA release in the nucleus accumbens (NAc), the prominent projection target of these neurons, has been implicated in reinforcement learning, motivation, aversion, and incentive salience. This contrast between heterogeneous functions of DA release versus a homogeneous role for DA neuron activity raises numerous questions regarding how VTA DA activity translates into NAc DA release. Further complicating this issue is increasing evidence that distinct VTA DA projections into defined NAc subregions mediate diverse behavioral functions. Here, we evaluate evidence for heterogeneity within the mesoaccumbal DA system and argue that frameworks of DA function must incorporate the precise topographic organization of VTA DA neurons to clarify their contribution to health and disease.

Neurodevelopment and efferocytosis have fascinated scientists for decades. How an organism builds a nervous system that is precisely tuned for efficient behaviors and survival and how it simultaneously manages constant somatic cell turnover are complex questions that have resulted in distinct fields of study. Although neurodevelopment requires the overproduction of cells that are subsequently pruned back, very few studies marry these fields to elucidate the cellular and molecular mechanisms that drive nervous system development through the lens of cell clearance. In this review, we discuss these fields to highlight exciting areas of future synergy. We first review neurodevelopment from the perspective of overproduction and subsequent refinement and then discuss who clears this developmental debris and the mechanisms that control these events. We then end with how a more deliberate merger ofneurodevelopment and efferocytosis could reframe our understanding of homeostasis and disease and discuss areas of future study.

Mounting evidence indicates that microglia, which are the resident immune cells of the brain, play critical roles in a diverse array of neurodevelopmental processes required for proper brain maturation and function. This evidence has ultimately led to growing speculation that microglial dysfunction may play a role in neurodevelopmental disorder (NDD) pathoetiology. In this review, we first provide an overview of how microglia mechanistically contribute to the sculpting of the developing brain and neuronal circuits. To provide an example of how disruption of microglial biology impacts NDD development, we also highlight emerging evidence that has linked microglial dysregulation to autism spectrum disorder pathogenesis. In recent years, there has been increasing interest in how the gut microbiome shapes microglial biology. In the last section of this review, we put a spotlight on this burgeoning area of microglial research and discuss how microbiota-dependent modulation of microglial biology is currently thought to influence NDD progression.

Depression is an episodic form of mental illness characterized by mood state transitions with poorly understood neurobiological mechanisms. Antidepressants reverse the effects of stress and depression on synapse function, enhancing neurotransmission, increasing plasticity, and generating new synapses in stress-sensitive brain regions. These properties are shared to varying degrees by all known antidepressants, suggesting that synaptic remodeling could play a key role in depression pathophysiology and antidepressant function. Still, it is unclear whether and precisely how synaptogenesis contributes to mood state transitions. Here, we review evidence supporting an emerging model in which depression is defined by a distinct brain state distributed across multiple stress-sensitive circuits, with neurons assuming altered functional properties, synapse configurations, and, importantly, a reduced capacity for plasticity and adaptation. Antidepressants act initially by facilitating plasticity and enabling a functional reconfiguration of this brain state. Subsequently, synaptogenesis plays a specific role in sustaining these changes over time.