Reviews & Analysis

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.

Recent progress in astrocyte biology requires a more cohesive conceptual framework. This Perspective introduces a ‘contextual guidance’ paradigm in which astrocytes are key to adaptive modeling of neural circuits in response to state changes.

Sleep is typically considered as a state of behavioral disconnection from the outside world. Recordings of brain activity and facial muscle tone during sleep reveal that humans can respond to external stimuli across most sleep stages. These windows of behavioral responsiveness reveal transient episodes of high-cognitive states with electrophysiological signatures suggestive of a conscious state.

This Review explains how the neural coding of uncertainty is theoretically conceived and empirically tested. It compares the approaches of two largely separate research communities and proposes goals for the field that combine these approaches.

We used single-nucleus sequencing to generate an atlas of gene expression and chromatin accessibility in the amygdala of outbred rats with divergent cocaine addiction-like behaviors. The results implicated dysregulation of metabolic pathways and GABAergic transmission as molecular bases of susceptibility or resistance to addiction.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that is driven by autoreactive lymphocytes. An in vivo CRISPR screen of T cell infiltration in a rat model of MS now identifies the genetic modules that control this key step in the immunopathology of MS.

Engelen et al. review in animals and humans how the CNS senses cardiac, respiratory and gastric rhythmic activity, and detail the range of cognitive functions impacted, from perceptual detection up to the sense of self.

Oligodendrocyte precursor cells (OPCs) are mostly known for their ability to differentiate into myelinating oligodendrocytes. Here, the authors discuss the multiple functions of OPCs beyond their precursor cell function in the healthy and diseased CNS.

We developed a 3D human neuroimmune axis model to study the interplay of brain innate immune cells and peripheral adaptive immune cells in Alzheimer’s disease. Alzheimer’s disease pathology induced a marked increase in CD8⁺ T cell infiltration, exacerbating neurodegeneration. The CXCL10–CXCR3 pathway has a key role in mediating this process.

Noh et al. show that the regulation of social behavior extends beyond neurons. Astrocytes, a major type of glial cell in the CNS, can influence social dominance behavior by modulating excitatory and inhibitory neural activities in the dorsomedial prefrontal cortex of adult male mice. This work highlights the importance of neuron–astrocyte interplay in controlling ethologically relevant behaviors.

Activating a specific subpopulation of glutamatergic neurons in the brainstem issues a motor command for global motor arrest. This motor arrest is distinct from defensive freezing and has a striking pause-and-play pattern accompanied by a reduction in respiration and heart rate.

Communication between diverse cell types is crucial to the development of the nervous system. However, the secreted signals that help to switch the cell fates of progenitor cells from neurogenesis to astrogenesis are not fully understood. Experiments in human tissues show that five ligands work together to push astrocyte generation and maturation.

Monteiro and colleagues used temperature manipulation to bidirectionally alter the speed of neuronal dynamics in the dorsal striatum of anesthetized rats. This manipulation selectively slowed down or sped up time perception, providing insights into the mechanisms of time-based decisions.

The Dominantly Inherited Alzheimer Network (DIAN) unites researchers aiming to understand autosomal dominant Alzheimer’s disease (ADAD). By longitudinally monitoring families worldwide, the DIAN Observational Study maintains an unprecedented resource of deeply phenotyped, freely available neuroimaging data on individuals with ADAD and their healthy relatives.