Nature Reviews Neuroscience最新文献

Understanding the relationship between genotype and neuronal circuit phenotype necessitates an integrated view of genetics, development, plasticity and learning. Challenging the prevailing notion that emphasizes learning and plasticity as primary drivers of circuit assembly, in this Perspective, we delineate a tripartite framework to clarify the respective roles that learning and plasticity might have in this process. In the first part of the framework, which we term System One, neural circuits are established purely through genetically driven algorithms, in which spike timing-dependent plasticity serves no instructive role. We propose that these circuits equip the animal with sufficient skill and knowledge to successfully engage the world. Next, System Two is governed by rare but critical ‘single-shot learning’ events, which occur in response to survival situations and prompt rapid synaptic reconfiguration. Such events serve as crucial updates to the existing hardwired knowledge base of an organism. Finally, System Three is characterized by a perpetual state of synaptic recalibration, involving continual plasticity for circuit stabilization and fine-tuning. By outlining the definitions and roles of these three core systems, our framework aims to resolve existing ambiguities related to and enrich our understanding of neural circuit formation.

Lipid metabolism encompasses the catabolism and anabolism of lipids, and is fundamental for the maintenance of cellular homeostasis, particularly within the lipid-rich CNS. Increasing evidence further underscores the importance of lipid remodelling and transfer within and between glial cells and neurons as key orchestrators of CNS lipid homeostasis. In this Review, we summarize and discuss the complex landscape of processes involved in lipid metabolism, remodelling and intercellular transfer in the CNS. Highlighted are key pathways, including those mediating lipid (and lipid droplet) biogenesis and breakdown, lipid oxidation and phospholipid metabolism, as well as cell–cell lipid transfer mediated via lipoproteins, extracellular vesicles and tunnelling nanotubes. We further explore how the dysregulation of these pathways contributes to the onset and progression of neurodegenerative diseases, and examine the homeostatic and pathogenic impacts of environment, diet and lifestyle on CNS lipid metabolism.

As one of the simplest and most evolutionarily conserved parts of the vertebrate nervous system, the spinal cord serves as a key model for understanding the principles of nervous system construction. During embryonic development, the spinal cord originates from a population of bipotent stem cells termed neuromesodermal progenitors, which are organized within a transient embryonic structure known as the neural tube. Neural tube morphogenesis differs along its anterior-to-posterior axis: most of the neural tube (including the regions that will develop into the brain and the anterior spinal cord) forms via the bending and dorsal fusion of the neural groove, but the establishment of the posterior region of the neural tube involves de novo formation of a lumen within a solid medullary cord. The early spinal cord primordium consists of highly polarized neural progenitor cells organized into a pseudostratified epithelium. Tight regulation of the cell division modes of these progenitors drives the embryonic growth of the neural tube and initiates primary neurogenesis. A rich history of observational and functional studies across various vertebrate models has advanced our understanding of the cellular events underlying spinal cord development, and these foundational studies are beginning to inform our knowledge of human spinal cord development.