Neuron最新文献

Cortical neurons are characterized by their variable spiking patterns. Here, we examine the specific hypothesis that cortical synchrony drives spiking variability in vivo. Using dynamic clamps, we demonstrate that intrinsic neuronal properties do not contribute substantially to spiking variability, but rather spiking variability emerges from weakly synchronous network drive. With large-scale electrophysiology, we quantify the degree of synchrony and its timescale in cortical networks in vivo. The timescale of synchrony shifts in a range from 25 to 200 ms, depending on the presence of external sensory input. In particular, when the network moves from spontaneous to driven modes, the synchrony timescales shift from slow to fast, leading to a natural reduction in response variability across cortical areas. Finally, while an individual neuron exhibits reliable responses to physiological drive, different neurons respond in a distinct fashion according to their intrinsic properties, contributing to stable synchrony across the neural network.

Stroke is a major cause of disability. Astrocytes respond to stroke in a gradated manner, but details of that response and its consequences for tissue repair are poorly understood, particularly across brain regions and stroke subtypes. We identified phenotypically and morphologically distinct zones of reactive astrocytes in mouse models of cortical and white matter stroke. Zone-specific transcriptomic analyses revealed that cortical, but not white matter, astrocytes upregulated transcriptional programs promoting the formation of new blood vessels, a key repair mechanism. Viral gain- and loss-of-function strategies showed that astrocytic Lamc1, in particular, is an endogenous mechanism by which cortical, but not white matter, astrocytes drive remodeling of larger-caliber brain microvessels. Exogenous induction of Lamc1 in white matter astrocytes improved vessel remodeling and repair and triggered differential T cell infiltration post stroke. Astrocyte subpopulations show region-specific responses to ischemia that can be leveraged to promote repair, including astrocyte-induced vascular remodeling.

The vasculature is increasingly recognized as an active regulator of homeostasis and repair, beyond conventional roles in nutrient delivery. In the central nervous system, vascular cells adopt region-specific traits tailored to the distinct demands of the brain, retina, and spinal cord. Despite long-standing interest in the spinal cord as a model for neural development and injury, its vascular organization and properties remain understudied. The assumption that spinal cord and brain neurovascular systems are built and function in the same way has limited progress. Here, we challenge this view by examining specific properties underlying spinal cord vascular development, physiology, and pathology. We highlight unique angioarchitecture and homeostatic mechanisms, and discuss how neurovascular disruption contributes to spinal disorders and regenerative failure after injury. Identifying critical knowledge gaps, we aim to stimulate new research in spinal cord neurovascular biology, redefining its importance for health and disease.

Stroke disrupts movement control by damaging descending motor pathways, yet the cortical dynamics underlying recovery remain poorly defined. Using a non-human primate model of primary motor cortex injury with impaired reach-to-grasp control, we examined how dorsal premotor cortex (PMd) activity supports recovery. Specifically, we studied the interaction between beta activity (12-30 Hz), often linked to "idle" states, and execution-related ensemble co-firing quantified with dimensionality reduction. Stroke impaired the temporal separability between beta bursts and movement-related co-firing, leading to slower reaction times and reduced performance. Recovery was associated with increased separability, and during grasping, beta activity progressively declined with recovery. These results indicate that reliable transitions between high-beta idle and high co-firing execution states are important for movement control, whereas pathological beta intrusions during execution degrade performance. Importantly, low-frequency alternating current stimulation (ACS) via a ringtrode interface enhanced temporal separability and improved reach-to-grasp performance, highlighting a potential therapeutic strategy.

Winner effects, where past victories enhance success, shape competition. In this issue of Neuron, Zheng et al.¹ show that female mice form hierarchies with weaker winner effects because prefrontal interneurons limit thalamic-prefrontal synaptic strengthening, revealing a framework for sex differences in social dominance.

Over the past decade, the PsychENCODE Consortium has transformed psychiatric genomics-from static maps of genetic risk to dynamic, cell-resolved models of the human brain-linking DNA sequence to neural circuitry and behavior and laying the foundation for precision approaches to mental illness.

Economic decision-making requires evaluating information about available options, such as their expected value and economic risk. Previous studies have shown that frontal cortical neurons encode these variables, but how this encoding is structured across different frontal regions and projection pathways remains unclear. We developed a decision-making task for head-fixed mice in which we varied the expected value and risk associated with reward-predicting stimuli. Using large-scale electrophysiology, two-photon imaging, and projection-specific optotagging, we identified distinct spatial gradients for these variables, with stronger expected value coding in dorsal frontal regions and stronger risk coding in medial regions. We then demonstrated that this encoding further depends on the neuronal projections: frontal neurons projecting to the dorsomedial striatum and claustrum differentially encoded economic variables. Our findings illustrate that frontal cortical representation of economic variables is jointly determined by spatial organization and downstream connectivity of neurons, revealing a structured, multi-scale code for economic variables.

The core use of human language is to send complex ideas from one mind to another. In everyday conversations, comprehension and production are intertwined, as speakers and listeners alternate roles. Nonetheless, the neural systems underlying these faculties are typically studied in isolation, using paradigms that cannot capture interactive communication. Here, we used fMRI hyperscanning to simultaneously record dyads engaged in real-time conversations. We used language model embeddings to quantify the degree to which production and comprehension systems rely on shared neural representations, both within and across brains. We found that both processes key into overlapping neural systems, with similar neural tuning for both processes, spanning the cortical language network. Speaker-listener coupling extended beyond the language network into areas associated with social cognition. Our results suggest that the neural systems for speech comprehension and production align with common linguistic features encoded in a broad cortical network for language and communication.

Patients with an ischemic stroke are often predisposed to emotional disorders. However, the mechanisms underlying post-stroke emotional disorders (PSEDs) remain unclear. Recent research highlights the role of neuroinflammation, driven primarily by infiltration of circulating immune cells within the brain parenchyma and accompanied by blood-brain barrier (BBB) disruption, in secondary emotional disorders. Combining human cohort and animal model data, we identified serum neutrophil extracellular traps (NETs) as significant contributors to PSEDs. Conditional knockout strategies and -omics analyses convergently identified central NETs as the specific modulator of PSEDs. We further elucidated that astrogliosis is catalyzed by lipocalin 2 (Lcn2) released from NETs, which constituted the core mechanism underlying PSEDs. Additionally, we provided proof-of-concept evidence that transcranial direct current stimulation (tDCS) can suppress Lcn2 release and alleviate PSEDs. Collectively, these findings delineated a distinct peripheral-central neuroimmune interaction pattern following BBB damage and highlighted the potential of non-invasive stimulation in effectively reshaping the neuroimmune environment.

Hippocampal ripples are highly synchronized neuronal population patterns reactivating past waking experiences in the offline brain. Whether the level, structure, and content of ripple-nested activity are consistent across consecutive events or are tuned in each event remains unclear. By profiling individual ripples using laminar currents in the mouse hippocampus during sleep/rest, we identified ripples in stratum pyramidale that feature current sinks in stratum radiatum (Rad^sink) versus stratum lacunosum-moleculare (LM^sink). These two ripple profiles recruit neurons differently. Rad^sink ripples integrate recent motifs of waking coactivity, combining superficial and deep CA1 principal cells into denser, higher-dimensional patterns that undergo hour-long stable reactivation. By contrast, LM^sink ripples contain core motifs of prior coactivity, engaging deep cells in sparser, lower-dimensional patterns that undergo a reactivation drift to gradually update their pre-existing content for recent wakefulness. We propose that ripple-by-ripple diversity supports parallel reactivation channels for integrating recent wakefulness while updating prior representations.