Communication between cells in the nervous system has long been understood to occur through chemical and electrical synapses, and through the release of signalling molecules and extracellular vesicles across the extracellular space. Intercellular nanotubes (NTs) — thin, membranous tubular bridges that physically connect distant cells — represent a structurally distinct route of communication, enabling the direct, targeted transfer of cellular cargoes between selected cells. Once studied almost exclusively in culture, NTs have now been visualized in situ and in vivo throughout the nervous system, including dendritic NTs between neurons, NTs formed by microglia and astrocytes, interpericyte NTs in the retina and NTs between satellite glia and peripheral sensory neurons. Through these connections, cells exchange mitochondria, proteins and their aggregates, and calcium, supporting three emerging roles: homeostatic rescue of stressed cells, pathological propagation of toxic proteins in neurodegeneration and non-synaptic calcium signalling, respectively. NT networks are dynamic and stress-responsive, suggesting that they provide a plastic infrastructure for resource sharing among neurons and glia. Understanding their function will require establishing a standardized definition, achieving rigorous in situ validation and quantification, and developing specific molecular tools to manipulate NTs. Intercellular nanotubes (NTs) provide a structurally distinct route of intercellular communication by enabling cellular material to be selectively transferred between cells. In this Review, Chang, Ryu and Kwon discuss the evidence for NT networks in the nervous system and the experimental approaches that can be used to study NTs in this context.
A population of acetylcholine-sensitive GABAergic neurons in the mouse hippocampus regulates sharp wave ripples and memory consolidation during sleep.
The mammalian cerebral cortex undergoes profound functional changes during early postnatal development. During this period, neurons generate spontaneous electrical activity long before sensory experience, coordinating into distinct patterns of synchronous activity. Traditionally, neuronal activity has been viewed as instructing interneuron development by modulating transcriptional programmes, morphology and connectivity. However, accumulating evidence in rodents reveals that this relationship is bidirectional: cortical interneurons are not merely passive recipients of activity-dependent signals but also active architects of developing network dynamics. They regulate spontaneous activity transitions from gap-junction-mediated synchronous events to large, synaptically driven bursts, and later to sparse firing characteristic of mature circuits. Critically, different interneuron subtypes mature at distinct timelines and orchestrate transitions in network activity. Activity-dependent mechanisms, in turn, regulate interneuron wiring, programmed cell death, diversification and terminal differentiation. This reciprocal dialogue between interneurons and network activity is essential for establishing functional cortical circuits. Neuronal activity is traditionally viewed as instructing cortical interneuron development. In this Review, Moissidis and Marín discuss how interneurons also actively shape early postnatal network activity, establishing a reciprocal dialogue that drives the maturation of both interneurons and cortical circuits.
Ageing is accompanied by a progressive decline in homeostatic resilience that increases vulnerability to chronic disease, disability and cognitive impairment. Although unhealthy brain ageing can often be prevented by managing the underlying risk factors, the molecular, cellular and physiological mechanisms that connect risk factors to late-life brain dysfunction remain incompletely understood. This review examines the role of the endocannabinoid system in brain ageing. The endocannabinoid system is a short-range lipid signalling network that helps to maintain neuronal, glial, metabolic and inflammatory homeostasis. Endocannabinoid signalling follows a dynamic lifespan trajectory, with relatively high activity during early adulthood and functional decline during ageing. Genetic or pharmacological disruption of endocannabinoid system activity impairs several processes linked to hallmarks of brain ageing, including neuroinflammatory control, adult neurogenesis, synaptic plasticity, cognitive performance, metabolic regulation and epigenetic stability. Conversely, low-dose Δ9-tetrahydrocannabinol (THC) treatment can ameliorate several ageing-related brain phenotypes in old animals. However, clinical evidence in older humans remains limited, and the therapeutic potential of cannabinoid-based interventions requires further evaluation. Age-related changes in endocannabinoid system (ECS) activity might contribute to the decline in cognitive function observed during ageing. In this review, Andreas Zimmer discusses how evidence from genetic and pharmacological studies in mice and humans indicate that relevant cognitive functions may change as a result of changing ECS activity.
A distinct neuropeptide Y2 receptor-expressing neuronal subtype is identified in the brainstem nucleus ambiguus that selectively projects to cardiac ganglia and regulates heart rate and the mammalian diving reflex.
