Annual review of neuroscience最新文献

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.

During rest and sleep, the brain processes information through replay, reactivating neural patterns linked to past events and facilitating the exploration of potential future scenarios. This review summarizes recent advances in understanding human replay and its biomarker, sharp-wave ripples (SPW-Rs). We explore detection methods and connect insights from rodent studies. The review highlights unique aspects of human replay in internal cognition such as prioritizing past experiences for offline learning, generating hypothesized solutions to current problems, and factorizing structural representations for future generalization. We also examine the characteristics of SPW-Rs in humans, including their distribution along the hippocampal longitudinal axis, their widespread brain activations, and their influence on internal cognitive processes. Finally, we emphasize the need for improved methodologies and technologies to advance our understanding of cognitive processes during rest and sleep.

To understand the pathophysiology of and develop effective therapeutics for brain disorders, some of which may involve uniquely human features of the nervous system, scalable human models of neural cell diversity and circuit formation are essential. The discovery of cell reprogramming and the development of approaches for generating stem cell-derived neurons and glial cells in 3D preparations known as neural organoids and assembloids, both in vitro and following transplantation in vivo, provide new opportunities to tackle these challenges. Here, we outline strengths and limitations of currently available human experimental models as applied to neurological and psychiatric disorders for both environmental and genetic risk factors, and we discuss how these new tools hold promise for accelerating the development of therapeutics.

Cognition unfolds dynamically over flexible timescales. A major goal of the field is to understand the computational and neurobiological principles that enable this flexibility. Here, we argue that the neurobiology of timing provides a platform for tackling these questions. We begin with an overview of proposed coding schemes for the representation of elapsed time, highlighting their computational properties. We then leverage the one-dimensional and unidirectional nature of time to highlight common principles across these coding schemes. These principles facilitate a precise formulation of questions related to the flexible control, variability, and calibration of neural dynamics. We review recent work that demonstrates how dynamical systems analysis of thalamocortical population activity in timing tasks has provided fundamental insights into how the brain calibrates and flexibly controls neural dynamics. We conclude with speculations about the architectural biases and neural substrates that support the control and calibration of neural dynamics more generally.

Many epidemiological studies have indicated that prenatal immune stress, frequently elicited by maternal immune activation, underlies a major risk for neuropsychiatric disorders of neurodevelopmental origin, such as schizophrenia and autism spectrum disorders. Animal models have been utilized to understand the biological processes of how immune stress influences brain development and resultant behavioral changes. Through such studies, the impacts of orchestrated immune-inflammatory mechanisms led by interleukin-6 (IL-6) on several developing cells, such as neural progenitors, neurons, and microglia, have been deciphered. In addition to prenatal immune stress from adverse maternal environments, mechanisms regulated by intrinsic factors directly associated with the offspring also exist. This review also introduces human stem cell models for addressing this topic and refers to potential modifiers of prenatal immune stress that could influence the eventual behavioral outcomes. Altogether, a mechanistic understanding of the impact of prenatal immune stress on brain development provides a fundamental addition in translational and clinical neurology and psychiatry.

Motor systems in animals are highly dependent on sensory information for optimal control and precision, with mechanosensory feedback from the somatosensory system playing a critical role. These mechanosensory pathways are woven into the descending feedforward pathways and local central pattern generator circuits that control and generate movement, respectively. Somatosensory feedback in mammals and insects, the two animal classes this review touches upon, is complex due to the increased demands that limbed locomotion, weight-bearing, and corrective movements place on sensorimotor control. In this review, we outline the salient features of the proprioceptive and exteroceptive sensory feedback pathways animals rely on for controlling movement and highlight some of the key principles of sensory feedback that are shared across the animal kingdom.

Life on this planet is heavily influenced by light, the most critical external environmental factor. Mammals perceive environmental light mainly through three types of photoreceptors in the retina-rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). The latest discovered ipRGCs are particularly sensitive to short-wavelength light and have a unique phototransduction mechanism, compared with rods and cones. Piles of evidence suggest that ipRGCs mediate a series of light-regulated physiological functions such as circadian rhythms, sleep, metabolic homeostasis, mood, development, and higher cognitions, collectively known as non-image-forming vision. Recent advances in systems neuroscience, driven by modern neural circuit tools, have illuminated the structure and function of the neural pathways connecting the retina to subcortical regions, highlighting their involvement in an array of non-image-forming functions. Here we review key discoveries and recent progress regarding the neural circuit mechanisms employed by ipRGCs to regulate diverse biological functions and provide insights into unresolved scientific questions in this area.

Because organisms are able to sense its passage, it is perhaps tempting to treat time as a sensory modality, akin to vision or audition. Indeed, certain features of sensory estimation, such as Weber's law, apply to timing and sensation alike. However, from an organismal perspective, time is a derived feature of other signals, not a stimulus that can be readily transduced by sensory receptors. Its importance for biology lies in the fact that the physical world comprises a complex dynamical system. The multiscale spatiotemporal structure of sensory and internally generated signals within an organism is the informational fabric underlying its ability to control behavior. Viewed this way, temporal computations assume a more fundamental role than is implied by treating time as just another element of the experienced world. Thus, in this review we focus on temporal processing as a means of approaching the more general problem of how the nervous system produces adaptive behavior.

Oligodendrocyte precursor cells (OPCs) are glia that give rise to myelinating oligodendrocytes in the developing and adult brain. However, emerging data suggest that OPCs perform a wide range of functions beyond oligodendrogenesis. For example, OPCs receive direct synaptic input from neurons, and they respond to neural activity through the release of factors that alter neuronal function. Moreover, OPCs directly associate with the neurovasculature to promote blood-brain barrier maintenance and integrity. Emerging data suggest that OPCs can refine synaptic connectivity during brain development, a process to which they contribute by phagocytosing synapses. Finally, OPCs are also involved in brain immunity, as they can adopt immune cell-like functions during demyelinating and neurodegenerative diseases. Altogether, these findings have identified OPCs as the major multitaskers of the brain. In this review, we discuss the roles of OPCs that extend beyond oligodendrocyte production and their relevance for neurological function.

Medulloblastoma is the most common malignant pediatric brain cancer and is broadly categorized into four molecular subgroups. Understanding the cell origins of medulloblastoma is crucial for preventing tumor formation and relapse. Recent single-cell transcriptomics studies have identified the potential cell lineage vulnerabilities and mechanisms underpinning malignant transformation in medulloblastoma. Emerging evidence suggests that genetic-epigenetic alterations specific to each subgroup lead to a lineage-specific stall in the neural developmental program and subsequent tumorigenesis. We discuss the putative cells of origin, plasticity, and heterogeneity within medulloblastoma subgroups and delve into the genetic and epigenetic changes that predispose cells to transformation. Additionally, we review the current insights into how cerebellar stem/progenitor cells and lineage plasticity impact medulloblastoma pathogenesis and highlight recent therapeutic advances targeting specific oncogenic vulnerabilities in this malignancy.