Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex

eLife, Год журнала: 2023, Номер 12

Опубликована: Апрель 27, 2023

Fluctuations in brain and behavioral state are supported by broadly projecting neuromodulatory systems. In this study, we use mesoscale two-photon calcium imaging to examine spontaneous activity of cholinergic noradrenergic axons awake mice order determine the interaction between arousal/movement transitions across dorsal cortex at distances separated up 4 mm. We confirm that GCaMP6s within axonal projections both basal forebrain locus coeruleus neurons track arousal, indexed as pupil diameter, changes engagement, reflected bouts whisker movement and/or locomotion. The broad coordination even distant segments indicates these systems can communicate, part, through a global signal, especially relation state. addition coordinated activity, also find evidence subpopulation may exhibit heterogeneity appears be independent our measures By monitoring interneurons cortex, found cells state-dependent (arousal/movement) activity. These results demonstrate provide prominent synchronized signal related state, therefore contribute cortical excitability.

Язык: Английский

---

The covariance environment defines cellular niches for spatial inference

Nature Biotechnology, Год журнала: 2024, Номер unknown

Опубликована: Апрель 2, 2024

A key challenge of analyzing data from high-resolution spatial profiling technologies is to suitably represent the features cellular neighborhoods or niches. Here we introduce covariance environment (COVET), a representation that leverages gene-gene covariate structure across cells in niche capture multivariate nature interactions within it. We define principled optimal transport-based distance metric between COVET niches scales millions cells. Using encode context, developed environmental variational inference (ENVI), conditional autoencoder jointly embeds and single-cell RNA sequencing into latent space. ENVI includes two decoders: one impute gene expression modality second project information onto data. can confer context genomics single dissociated outperforms alternatives for imputing on diverse datasets.

Язык: Английский

---

Inhibitory specificity from a connectomic census of mouse visual cortex

Nature, Год журнала: 2025, Номер 640(8058), С. 448 - 458

Опубликована: Апрель 9, 2025

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties1. Synaptic connectivity shapes how type participates in the cortical circuit, but mapping rules at resolution distinct types remains difficult. Here we used millimetre-scale volumetric electron microscopy2 to investigate all inhibitory neurons across densely segmented population 1,352 cells spanning layers mouse visual cortex, producing wiring diagram inhibition more than 70,000 synapses. Inspired by classical neuroanatomy, classified based on targeting dendritic compartments developed an excitatory neuron classification reconstructions whole-cell maps synaptic input. Single-cell showed class disinhibitory specialist that targets basket cells. Analysis onto found widespread specificity, many interneurons exhibiting differential spatially intermingled subpopulations. Inhibitory was organized into 'motif groups', diverse sets collectively target both perisomatic same targets. Collectively, our analysis identified new organizing principles for will serve as foundation linking contemporary multimodal atlases diagram.

Язык: Английский

---

Connectomics of predicted Sst transcriptomic types in mouse visual cortex

Nature, Год журнала: 2025, Номер 640(8058), С. 497 - 505

Опубликована: Апрель 9, 2025

Neural circuit function is shaped both by the cell types that comprise and connections between them1. have previously been defined morphology2,3, electrophysiology4, transcriptomic expression5,6, connectivity7-9 or a combination of such modalities10-12. The Patch-seq technique enables characterization morphology, electrophysiology properties from individual cells13-15. These were integrated to define 28 inhibitory, morpho-electric-transcriptomic (MET) in mouse visual cortex16, which do not include synaptic connectivity. Conversely, large-scale electron microscopy (EM) morphological reconstruction near-complete description neuron's local connectivity, but does electrophysiological information. Here, we leveraged information predict transcriptomically subclass and/or MET-type inhibitory neurons within EM dataset. We further analysed Martinotti cells-a somatostatin (Sst)-positive17 type18,19-which classified successfully into Sst MET-types with distinct axon myelination output connectivity patterns. demonstrate features can be used link across experimental modalities, enabling comparison gene expression electrophysiology. observe unique rules for predicted types.

Язык: Английский

---

An inhibitory gate for state transition in cortex

eLife, Год журнала: 2017, Номер 6

Опубликована: Май 16, 2017

Large scale transitions between active (up) and silent (down) states during quiet wakefulness or NREM sleep regulate fundamental cortical functions are known to involve both excitatory inhibitory cells. However, if how inhibition regulates these activity is unclear. Using fluorescence-targeted electrophysiological recording cell-specific optogenetic manipulation in anesthetized non-anesthetized mice, we found that two major classes of interneurons, the parvalbumin somatostatin positive cells, tightly control up-to-down down-to-up state transitions. Inhibitory regulation transition was observed under natural optogenetically-evoked conditions. Moreover, perturbative experiments revealed interneuron-type specific. Finally, local small ensembles interneurons affected populations millimetres away from modulated region. Together, results demonstrate potently gates states, reveal cellular mechanisms by which microcircuits at mesoscale.

Язык: Английский

---