Reviews & Analysis

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.

Brain connections modulated by 534 deep-brain-stimulation electrodes revealed a gradient of circuits involved in dystonia, Parkinson’s disease, Tourette’s syndrome and obsessive-compulsive disorder. Together, these circuits begin to describe the human ‘dysfunctome’, a library of dysfunctional circuits that lead to various brain disorders.

Long COVID has remained an on-going public health issue in the years following the global pandemic. Here, we report blood–brain barrier disruption in patients with acute SARS-CoV-2 infection and brain fog, and patients presenting with long COVID, brain fog and cognitive decline, compared to those with long COVID without any neurological symptoms.

The Sehgal lab presents data showing that the non-cell autonomous pathway of glial lipid droplet formation occurs during sleep and helps to resolve neuronal reactive oxygen species (ROS). This promotes neuronal function after an active day. Hence, this pathway has an important physiological function beyond its previously described role in ROS-associated diseases, including Alzheimer’s disease.

Both caloric restriction and obesity affect autoimmune diseases. The activation of brainstem neurons in the ventrolateral medulla (VLM) with fasting suppresses experimental autoimmune diseases. Stimulation of VLM neurons alters T cell traffic by redistributing immune cells to bone marrow and reduces inflammatory cytokine production, thus providing therapy of experimental autoimmunity.

Muller et al. demonstrate that reward signals recorded from the frontal cortex of nonhuman primates exhibit a population-based scheme for learning probability distributions over reward values. This study provides evidence that neural signals outside of the midbrain reflect the principles of distributional reinforcement-learning theory.

A widespread group of cerebellar projections form monosynaptic excitatory synapses with neurons throughout the substantia nigra pars compacta (SNc). These projections contain information associated with movement and reward and can rapidly increase SNc neuron activity, and thereby basal ganglia dopamine levels, which contribute to movement initiation, vigor and reward processing.

This research elucidates that oligodendrocytes detect and respond to fast axonal spiking through K⁺ signaling, and that Kir4.1 channel activation has a pivotal role. This activity-driven interaction regulates axonal metabolic support by oligodendrocytes and influences lactate delivery and glucose metabolism in axons, which is essential for sustaining axonal health.

Using in vivo imaging in zebrafish, we unveiled critical components (PSD-95, gephyrin and neuroligin-3) and dynamic properties of synapses between neurons and oligodendrocyte precursor cells (OPC). Furthermore, we showed that neuron–OPC synapses have a pivotal role in regulating OPC development and CNS myelination.

Fang and Creed review and synthesize recent studies of the striatum and pallidal complex. Based on connectivity and organization of striatal–pallidal pathways in rodents, they propose how these structures coordinate learning and flexible behavior.

We show that genetic disruption of TFEB- and vacuolar ATPase-mediated lysosomal signaling leads to increased tau pathology and defective microglia activation. Our findings demonstrate an essential role of the lysosome in regulating microglia activity in tauopathy and Alzheimer’s disease.

We discovered expression of SYNGAP1, which encodes the ‘synaptic’ protein SYNGAP1, within human cortical progenitors. In an organoid model of SYNGAP1 haploinsufficiency, cortical neurogenesis and neuronal network activity were disrupted. This finding reveals an unknown function for SYNGAP1 at early stages of development, providing a new framework for understanding the pathophysiology of autism spectrum disorder.

Recent discoveries highlight the skull bone marrow, linked to the CNS via osseous channels, as a key neuroimmune compartment. Here, the authors discuss the anatomy, functions and implications of this immune reservoir on CNS health and disease.

This paper characterizes two distinct philosophies underlying previous work on how Bayesian computations are linked to neural data, highlighting how different theories may be motivated by different tacit assumptions and thereby explain different data.

Neuroscientists have long believed that hunger increases activity in agouti-related peptide (AgRP) neurons to regulate feeding-related behaviors and metabolism, but a new study shows that the story is much more complicated. Sayar-Atasoy and colleagues show that the time of day uncouples activity in AgRP neurons from hunger and demonstrate how daily feeding patterns influence future AgRP neuron activity.

Despite diversity, equity and inclusion efforts, women remain underrepresented as academic leaders in neuroscience. In this Perspective, Bourke, Spanò and Schuman discuss current European initiatives and propose further actions to support women’s career progression in STEM.