Annual review of neuroscience最新文献

Astrocytes, the bushy, star-shaped glial cells of the brain and spinal cord, support the proper development and function of many cells in the central nervous system. In response to disease or injury they transform, adopting varied morphologies, molecular signatures, and functions-this state of transformation is known as reactivity. For over a century, the reactivity of astrocytes has been recognized, but it is the recent surge in technological innovation that has shed light on the diverse nature of this reactivity. It is this developing understanding of the heterogeneity of reactive astrocytes across disease-specific contexts and a spatiotemporal gradient that now excites the astrocyte field. In this review, we discuss the current understanding of reactive astrocyte heterogeneity, highlight the biological implications of this heterogeneity, and propose future approaches to aid in fully understanding the heterogeneity of reactive astrocytes.

Thirst and hunger drives are fundamental survival mechanisms that transform physiological need into motivated behavior. In the brain, discrete types of circumventricular and hypothalamic neurons serve as neural circuit elements underlying thirst and hunger drives. These neurons receive signals of dehydration and starvation arising from outside the brain and communicate these homeostatic needs to downstream neural circuit elements. Recent advances in neural circuit activity recording and control in behaving mammals have elucidated how direct and indirect targets of these cells encode goal-relevant, affective, autonomic, and behavioral components of the drives, resulting in a finely tuned, robust, and flexible set of survival-appropriate behaviors.

Locomotion, like all behaviors, possesses an inherent flexibility that allows for the scaling of movement kinematic features, such as speed and vigor, in response to an ever-changing external world and internal drives. This flexibility is embedded in the organization of the spinal locomotor circuits, which encode and decode commands from the brainstem and proprioceptive feedback. This review highlights our current understanding of the modular organization of these locomotor circuits and how this modularity endows them with intrinsic mechanisms to adjust speed and vigor, thereby contributing to the flexibility of locomotor movements.

The cerebral cortex, a brain structure that is responsible for higher-order cognitive functions, contains hundreds of distinct cell types distributed across dozens of anatomical and functional areas. These cells emerge from a limited set of progenitor cell types during early development through a stereotypic series of neurodevelopmental events that include patterning, neurogenesis, migration, and maturation. High-throughput single-cell and spatial genomics have enabled the systematic discovery of molecular signatures underlying the formation of the cerebral cortex in mammals, including primates and humans. Here, we review the major principles underlying the processes through which the remarkable diversity of cell types known to exist in the adult cerebral cortex emerges during early development and contextualize the molecular signatures of cell types in their forms, functions, and states that have been uncovered through recent transcriptomic studies. We discuss the challenges associated with the use of static measurements to capture the dynamics of development.

Astrocytes, traditionally viewed as supportive cells within the central nervous system (CNS), are now recognized as dynamic regulators of neural signaling and homeostasis. They actively engage in synaptic transmission and brain health by releasing gliotransmitters such as glutamate, GABA, ATP, adenosine, lactate, and d-serine. Astrocytes also play a critical role in ion homeostasis and immune response through cytokine modulation and reactive oxygen species regulation. In pathological states, astrocytes can become reactive, contributing to neurodegeneration through dysregulated gliotransmitter release and metabolic dysfunction. Recently developed molecular and pharmacological tools allow the exploration of astrocytic response to injury and its influence on neuronal function. This review explores the multifaceted roles of astrocytes in health and disease, emphasizing sensory and motor functions as well as various neurological and psychiatric disorders. Understanding astrocyte-neuron signaling in health and disease provides crucial insights into their dual roles, offering novel avenues for therapeutic interventions in CNS disorders.

Deep brain stimulation (DBS), a method in which electrical stimulation is delivered to specific areas of the brain, is an effective treatment for managing symptoms of a number of neurological and neuropsychiatric disorders. Clinical access to neural circuits during DBS provides an opportunity to study the functional link between neural circuits and behavior. This review discusses how the use of DBS in Parkinson's disease and dystonia has provided insights into the brain networks and physiological mechanisms that underlie motor control. In parallel, insights from basic science about how patterns of electrical stimulation impact plasticity and communication within neural circuits are transforming DBS from a therapy for treating symptoms to a therapy for treating circuits, with the goal of training the brain out of its diseased state.

Auditory processing in mammals begins in the peripheral inner ear and extends to the auditory cortex. Sound is transduced from mechanical stimuli into electrochemical signals of hair cells, which relay auditory information via the primary auditory neurons to cochlear nuclei. Information is subsequently processed in the superior olivary complex, lateral lemniscus, and inferior colliculus and projects to the auditory cortex via the medial geniculate body in the thalamus. Recent advances have provided valuable insights into the development and functioning of auditory structures, complementing our understanding of the physiological mechanisms underlying auditory processing. This comprehensive review explores the genetic mechanisms required for auditory system development from the peripheral cochlea to the auditory cortex. We highlight transcription factors and other genes with key recurring and interacting roles in guiding auditory system development and organization. Understanding these gene regulatory networks holds promise for developing novel therapeutic strategies for hearing disorders, benefiting millions globally.

The cerebral cortex performs computations via numerous six-layer modules. The operational dynamics of these modules were studied primarily in early sensory cortices using bottom-up computation for response selectivity as a model, which has been recently revolutionized by genetic approaches in mice. However, cognitive processes such as recall and imagery require top-down generative computation. The question of whether the layered module operates similarly in top-down generative processing as in bottom-up sensory processing has become testable by advances in the layer identification of recorded neurons in behaving monkeys. This review examines recent advances in laminar signaling in these two computations, using predictive coding computation as a common reference, and shows that each of these computations recruits distinct laminar circuits, particularly in layer 5, depending on the cognitive demands. These findings highlight many open questions, including how different interareal feedback pathways, originating from and terminating at different layers, convey distinct functional signals.

In the natural world, animals make decisions on an ongoing basis, continuously selecting which action to undertake next. In the lab, however, the neural bases of decision processes have mostly been studied using artificial trial structures. New experimental tools based on the genetic toolkit of model organisms now make it experimentally feasible to monitor and manipulate neural activity in small subsets of neurons during naturalistic behaviors. We thus propose a new approach to investigating decision processes, termed reverse neuroethology. In this approach, experimenters select animal models based on experimental accessibility and then utilize cutting-edge tools such as connectomes and genetically encoded reagents to analyze the flow of information through an animal's nervous system during naturalistic choice behaviors. We describe how the reverse neuroethology strategy has been applied to understand the neural underpinnings of innate, rapid decision making, with a focus on defensive behavioral choices in the vinegar fly Drosophila melanogaster.

Predictive processing is a computational framework that aims to explain how the brain processes sensory information by making predictions about the environment and minimizing prediction errors. It can also be used to explain some of the key symptoms of psychotic disorders such as schizophrenia. In recent years, substantial advances have been made in our understanding of the neuronal circuitry that underlies predictive processing in cortex. In this review, we summarize these findings and how they might relate to psychosis and to observed cell type-specific effects of antipsychotic drugs. We argue that quantifying the effects of antipsychotic drugs on specific neuronal circuit elements is a promising approach to understanding not only the mechanism of action of antipsychotic drugs but also psychosis. Finally, we outline some of the key experiments that should be done. The aims of this review are to provide an overview of the current circuit-based approaches to psychosis and to encourage further research in this direction.