Reviews & Analysis

In Caenorhabditis elegans, loss of the transcription factors FOS-1 and EGL-43 — orthologs of human FOS and MECOM, respectively — severely reduces presynaptic gene expression in dopaminergic neurons. These transcription factors form an activity-regulated positive feedback loop, which modulates the expression of synaptic genes and genetic programs to promote synapse formation.

Task demands are a primary determiner of behavior and neurophysiology. Here the authors discuss how understanding their influence through multitask studies and tests of generalization is the key to articulating novel cognitive neuroscience concepts.

The hypothesis that dopamine reports reward prediction errors has been both influential and controversial. This Perspective characterizes the present state of evidence, indicating where it succeeds and where it falls short. A complete account of dopamine will probably need to move beyond the reward prediction error hypothesis while retaining its core explanatory power.

Independent of its appetite- and body weight-modulating effects, the hormone asprosin activates its receptor PTPRD at cerebellar Purkinje neurons to enhance thirst and maintain fluid homeostasis. Surprisingly, this has no effect whatsoever on Purkinje neuron-mediated motor coordination and learning.

Neurons in the hippocampus of Egyptian fruit bats modulate their activity during a spatial reward task depending on the identity of the human experimenter at the goal location. A separate subpopulation of neurons carries significant spatial information about the positions and identities of humans traversing the same environment while bats are stationary.

Recent studies suggest a close interaction between sensory and motor processes across the neocortex. In this Perspective, Rao proposes active predictive coding as a sensory–motor theory that explains the structure of the neocortex as well as some of its diverse computational capabilities.

We present a developmental atlas that offers insight into sequential epigenetic changes underlying early human brain development modeled in organoids, which reconstructs the differentiation trajectories of all major CNS regions. It shows that epigenetic regulation via the installation of activating histone marks precedes activation of groups of neuronal genes.

Astrocytes have important roles in the repair of the CNS. However, the underlying mechanisms involved remain incompletely understood. O’Shea et al. report that the functional reprogramming of astrocytes at the borders of traumatic lesions contributes to the re-establishment of CNS integrity by separating the parenchyma from stromal and immune cells.

This Review provides a framework for incorporating APOE into Alzheimer’s disease (AD) clinical care by bridging recent advances in APOE and AD research with emerging clinical applications for APOE testing and ApoE-targeted therapies.

Cognitive control is crucial for present and future success and therefore is a frequent target of interventions. This study showed that training cognitive control in a large sample of 6–13-year-old children did not lead to any behavioral or neural changes, either immediately or 1 year after training.

After spinal cord injury, stromal fibroblasts originate from pericytes and perivascular fibroblasts, with pericytes more prevalent in gray matter and fibroblasts in white matter. Holl et al. show that both cell types respond to injury and inflammation, are activated, and transcriptionally converge on scar formation after injury, paving the way for therapeutic possibilities.

Specifically mutating the neurofibromatosis type 1 gene (NF1) in oligodendrocyte precursor cells (OPCs) impairs their adaptive response to neuronal activity and their differentiation into mature oligodendrocytes, as well as promoting focal regions of OPC hyperdensity. These defects delay oligodendroglial development and impede adaptive oligodendrogenesis, which are important for motor learning.

Mature myelin has been considered static, though recent evidence indicates it is in fact dynamic. Here, Osso and Hughes review the dynamics of mature myelin, a form of neuroplasticity, from myelin turnover to remodeling of myelin structure. The authors consider the mechanisms that regulate these dynamics and the functional implications of mature myelin remodeling.

By using genetic admixture in the multi-omic analysis of postmortem brains from Black Americans, we show that genetic ancestry influences gene expression in the brain. Notably, we find enrichment of ancestry-associated genes for immune response and vascular function, but not neuronal function. Our findings have potential implications for stroke, Parkinson’s disease and Alzheimer’s disease.

Nongenetic factors contribute to the onset, progression and severity of neurodegenerative diseases. Here, the authors describe how exposomics, the systematic analysis of environmental factors, can help neuroscientists understand these diseases.

Gene expression in the human cortex is shown to exhibit a generalizable three-component architecture that reflects neuronal, metabolic, and immune programmes of healthy brain development. The three components have distinct associations with autism spectrum disorder and schizophrenia, revealing connections between previously unrelated results from studies of case–control neuroimaging, differential gene expression, and genetic risk.

In the first comprehensive mRNA isoform atlas of the developing and adult mouse brain, we discover that region and age influence the isoform repertoire of cell subtypes. We link peak cell type regulation to the critical development period and report attenuated levels in adulthood.

This paper provides recommendations for researchers on responsibly conceptualizing, contextualizing and communicating issues related to race and ethnicity, including examples of important terms and frameworks.

Cold sensor identities in peripheral somatosensory neurons remain obscure. We show that GluK2, a kainate-type glutamate-sensing chemoreceptor that mediates synaptic transmission in the brain, mediates the sensing of cold but not cool temperatures in mouse dorsal root ganglia neurons in the periphery. Thus, we identify GluK2 as a cold-sensing thermoreceptor.

Astrocytes have important roles in disease and are difficult to modulate, owing to a paucity of known targets. Clayton et al. develop a screening platform to unbiasedly identify modulators of astrocyte reactivity. They discover that HDAC3 inhibitors regulate astrocyte transitions into their reactive phenotype in vitro and in vivo.