Search

To mark the 20th anniversary of Nature Reviews Neuroscience, in this Viewpoint article we asked some of the researchers who have authored pieces published in the journal in recent years for their views on how the field, and their areas within it, have developed over the past two decades.

In this manuscript, the authors use state-of-the-art imaging methods to report the discovery of novel forms of astrocyte calcium signaling in wild-type mice and in mutant mice previously thought to lack astrocyte calcium dynamics. The findings have important implications for experimental and theoretical studies of astrocyte functions in neural circuits.

The cell biological mechanisms that govern myelin sheath extension remain incompletely understood. Here, the authors find that calcium signaling in oligodendrocytes is required for the actin-dependent extension of myelin sheaths.

Neuronal activity increases local cerebral blood flow (CBF) to satisfy metabolic demand, yet the role of astrocytes in this phenomenon is controversial. Here, the authors show that astrocytes amplify CBF only when neuronal activity is sustained.

Cannabis exposure is a critical concern, particularly during adolescence. This study shows that tetrahydrocannabinol-induced cognitive deficits are mediated by a specific astrocytic ensemble in the nucleus accumbens whose manipulation prevents and reverses these effects.

In mice, a population of astrocytes in the central striatum, characterized by expression of μ-crystallin, has a role in perseveration phenotypes that are often associated with human neuropsychiatric disorders.

ATP has essential roles in cell signalling and energy homeostasis and biosensors to detect it have many potential applications. Here, the authors develop a new ATP sensor that can be targeted to the membrane or cytosol.

This Review article by Baljit Khakh and Michael Sofroniew discusses the latest progress in demonstration of molecular, cellular and functional heterogeneity of astrocytes in the central nervous system. The article highlights the way in which this diversity within and across astrocytes can affect normal function of the brain differently, and discusses pathological conditions where astrocyte heterogeneity is instrumental in manifesting various aspects of CNS dysfunction.

In this study, the authors show that altered medium spiny neuron excitability and symptom onset in Huntington's disease model mice is associated with decreased expression of Kir4.1 and impaired K⁺ handling by astrocytes. Exogenous expression of Kir4.1 could partially rescue motor function and prolong survival in HD mice.

Aging drives distinct molecular changes in the brain. Here, the authors use scRNAseq and MERFISH and find that in mice, aging induces subtype-specific, regionally biased changes in striatal astrocytes, marked by transcriptional repression, inflammation, and impaired neuronal interactions.

Human and mouse astrocytes express the protocadherin PcdhγC3, which promotes self-recognition of individual astrocytes, thereby contributing to normal astrocyte and brain development.

Analyses of the proteomes of astrocytes and neurons in a cell-specific and subcompartment-specific manner reveal distinct roles for these cell types that are relevant to obsessive–compulsive disorder and perhaps other brain disorders.

A protocol detailing the labeling and identification of cell- and subcompartment-specific proteins found within intact astrocytes and neurons in vivo using the proximity-dependent biotinylation system BioID2.

Periaqueductal gray (PAG) inputs control hunting, but foraging-inducing PAG cells were unidentified. Here, authors show that in mice activity in the projection of vgat PAG cells to the zona incerta is sufficient and necessary for food-seeking.

Shuman et al. report that epileptic mice harbor desynchronized hippocampal interneuron activity and unstable spatial representations, revealing that precise intrahippocampal synchronization is critical for spatial coding.

Much progress has been made in understanding astrocytes, but details on their functions and interactions remain difficult to determine. Yu, Nagai and Khakh give an overview of recent advances in the toolbox for molecular, genetic, morphological and physiological investigations into astrocytes.

Enduring changes in synaptic efficacy are highly sensitive to stress. Here, the authors show that astrocytic delivery of metabolites has an important role in the stress-mediated impairment of synaptic plasticity.

Sustained delivery of axon-specific growth factors not typically present in spinal cord lesions allows for robust axonal regrowth only if the astrocytic scar is present—a result that questions the prevailing dogma and suggests that astrocytic scarring aids rather than prevents central nervous system axon regeneration post injury.

Using a membrane-tethered, genetically encoded Ca²⁺ indicator, the authors describe a novel Ca²⁺ signal in hippocampal astrocytes. These 'spotty' Ca²⁺ signals were found to be mediated by astrocytic TRPA1 channels. Decreasing astrocyte resting Ca²⁺, regulated by TRPA1 channels, decreased interneuron inhibitory synapse efficacy by reducing GABA transport through GAT-3.

One major challenge in neuroscience is to uncover how defined neural circuits in the brain encode, store, modify, and retrieve information. Meeting this challenge comprehensively requires tools capable of recording and manipulating the activity of intact neural networks in naturally behaving animals. Head-mounted miniature microscopes are emerging as a key tool to address this challenge. Here we discuss recent work leading to the miniaturization of neural imaging tools, the current state of the art in this field, and the importance and necessity of open-source options. We finish with a discussion on what the future may hold for miniature microscopy.

Understanding the role of astrocytic calcium signals has been hindered by our inability to measure calcium in small volume compartments. Here, the authors develop a technique to do this by modifying the genetically encoded calcium sensor GCaMP2 to ensure greater expression near the membrane.

Good–bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.