Neuron最新文献

Understanding how behavior modulates neuronal integration is a fundamental goal in neuroscience. We combined voltage imaging with optogenetics to reveal how excitatory (E) and inhibitory (I) inputs modulate spiking output, subthreshold dynamics, and gain in genetically defined CA1 neurons. We imaged pyramidal cells (PCs), vasoactive intestinal peptide (VIP), somatostatin (SST), and parvalbumin (PV) interneurons (INs) and found that locomotion reduced firing in PCs and VIP INs while increasing activity in SST and PV INs. Prolonged optical depolarization revealed that inhibitory inputs substantially contribute to intracellular theta oscillations in PCs and VIP cells. Firing rate-laser intensity (F-I) curves revealed distinct gain modulation across cell types, with a divisive gain reduction in PC bursting during locomotion, while simple spikes are unaffected. A two-compartment model suggested that this effect results from a balanced increase in E/I input to the soma and dendrite. These findings reveal how behavior coordinates E/I signaling to modulate hippocampal computations.

Feeding behavior is tightly regulated by circadian rhythms, and disruption of this coordination promotes mistimed eating and metabolic dysfunction. Here, using mouse models, we identify a noncanonical role of neuropeptide Y-expressing interneurons (NPY-INs) in the ventral hippocampus (vHPC) in circadian feeding control. vHPC NPY-INs exhibit robust diurnal activity fluctuations that are lost under chronic circadian disruption. Functionally, these neurons regulate feeding across the day-night cycle by engaging distinct transmitters: NPY signaling predominates during the light phase, whereas gamma-aminobutyric acid (GABA) signaling dominates during the dark phase. Furthermore, vHPC NPY-INs receive monosynaptic glutamatergic and GABAergic inputs from the medial preoptic area (MPOA), which confer circadian plasticity, and project to the ventral subiculum (vSub), where NPY₁R and NPY₂R signaling mediates feeding behavior. Together, these findings identify the vHPC NPY-INs as a critical hub linking circadian regulation and energy balance, offering new insight into neural mechanisms underlying mistimed feeding and metabolic disorders.

Parallel visual processing begins with retinal bipolar cells, traditionally regarded as independent chemical synaptic channels. However, the circuit-level synaptic integration of chemical and electrical synapses within this network remains unclear. Using dual patch-clamp recordings and two-photon imaging in whole-mount retina, we systematically characterized synaptic transmission across 13 mouse and 2 human cone bipolar cell (CBC) types, revealing two distinct modes: a fast, direct chemical pathway and a slower, serial electrical-chemical circuit among both ON and OFF CBCs. In mice, the slow mode generates spatially dispersed glutamate "clouds" that facilitate integration across CBC types. We discovered specific "driver" CBCs that distribute robust, sustained signals through a hierarchical, functionally rectified network, enhancing sensitivity to small, low-contrast stimuli in downstream retinal cells and thalamic neurons in awake mice. Our findings challenge the classical view of independent CBC channels, revealing an integrative, hierarchical electrical-chemical synaptic architecture that enhances visual detection and coding efficiency.

The suprachiasmatic nucleus (SCN) is considered the master pacemaker of the circadian clock in mammals, but our current knowledge of the SCN is mostly based on rodent studies. Here, we report a comprehensive molecular and cellular atlas for the adult human SCN by spatial transcriptomics, single-nucleus RNA sequencing, and deep-learning-based histological analysis. We identified seven human SCN neuron subtypes with specific transcriptomes and spatial distributions. Comparison of humans, mice, and non-human primates revealed the conserved functional segregation within the SCN regulated by LIM homeobox 1 (LHX1) and RAR-related orphan receptor B (RORB). Furthermore, our results suggested that the human SCN has undergone marked reorganization of its neuropeptide signaling network. Finally, integrative analysis of human SCN transcriptomes and genome-wide association studies (GWASs) identified arginine vasopressin (AVP)/neuromedin S (NMS) subtype as the potential neuronal correlate for morningness chronotype. Thus, our spatial and single-cell transcriptomic atlas of the human SCN provided a basis for the understanding of neural and molecular mechanisms of the human circadian clock.

Synapse formation and elimination are two crucial processes that occur concurrently in the developing brain. Astrocytes and microglia control both processes, yet how these two major glial cell types of the central nervous system (CNS) communicate to balance synapse formation and elimination is unknown. Astrocytes secrete the synaptogenic protein Hevin/SPARCL1, which induces the formation and plasticity of thalamocortical synapses in the mouse visual cortex. Here, we found that, in addition to this synaptogenic function, Hevin directly signals to microglia by interacting with Toll-like receptor 4 (TLR4). This signaling occurs when Hevin is proteolytically cleaved, producing a C-terminal fragment that is no longer synaptogenic. We found that Hevin, through TLR4, induces a distinct microglial state defined by increased TLR2 expression and phago-lysosomal content in vitro and in vivo. Microglial TLR4 signaling is required for the proper elimination of thalamocortical synapses during early postnatal development.

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.

Myelin thickness and internode length are matched to axon caliber in the central nervous system (CNS), critical for optimal axonal action potential conduction. Dereddi et al.¹ show that mechanotransduction channel TMEM63A in oligodendrocytes couples membrane stretch to Ca²⁺ signaling to refine myelin architecture.

Shammas et al.¹ report that LCMV infection epigenetically primes hippocampal neurons for heightened responses to viral rechallenge, driving synaptopathy. These findings suggest epigenetic inflammatory memory in neurons, resembling previous observations in other CNS non-immune cells, and may guide therapeutic interventions.

To pursue a moving visual object, the brain must continuously steer the object to the center of the visual field via feedback. The gain of this control loop is flexible, yet the biological mechanisms underlying such adaptive control are not well understood. Here, we show that adaptive control in the Drosophila pursuit system involves two parallel pathways. One detects objects in the periphery and steers them toward the center of the visual field. The other detects objects near the center of the visual field and steers them to the visual midline while also increasing forward velocity. This latter pathway is flexible: gain increases when the object is moving away from the midline and when the pursuer is running fast-situations that demand rapid steering-and this pathway is preferentially recruited during arousal. Our findings demonstrate how adaptive control can emerge from parallel sensory-motor pathways with specialized properties.