Cell-type-specific inhibitory circuitry from a connectomic census of mouse visual cortex

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 24, 2023

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties. Synaptic connectivity powerfully shapes how type participates in the cortical circuit, but mapping rules at resolution distinct types remains difficult. Here, we used millimeter-scale volumetric electron microscopy 1 to investigate all inhibitory neurons across densely-segmented population 1352 cells spanning layers mouse visual cortex, producing wiring diagram connections more than 70,000 synapses. Taking data-driven approach inspired by classical neuroanatomy, classified based on relative targeting dendritic compartments other developed novel classification excitatory morphological synaptic input The between revealed class disinhibitory specialist basket cells, addition familiar subclasses. Analysis onto found widespread specificity, many interneurons exhibiting differential certain subpopulations spatially intermingled potential targets. Inhibitory was organized into “motif groups,” diverse sets that collectively target both perisomatic same Collectively, our analysis identified new organizing principles for inhibition will serve as foundation linking modern multimodal atlases diagram.

Language: Английский

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The covariance environment defines cellular niches for spatial inference

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: April 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.

Language: Английский

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Functional specialization of hippocampal somatostatin-expressing interneurons

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(17)

Published: April 19, 2024

Hippocampal somatostatin-expressing ( Sst ) GABAergic interneurons (INs) exhibit considerable anatomical and functional heterogeneity. Recent single-cell transcriptome analyses have provided a comprehensive -IN subpopulations census, plausible molecular ground truth of neuronal identity whose links to specific functionality remain incomplete. Here, we designed an approach identify access -INs based on transcriptomic features. Four mouse models single or combinatorial Cre- Flp- expression differentiated functionally distinct CA1 hippocampal Sst- INs that largely tiled the morpho-functional parameter space superfamily. Notably, Sst;;Tac1 intersection revealed population bistratified preferentially synapsed onto fast-spiking (FS-INs) were sufficient interrupt their firing. In contrast, Ndnf;;Nkx2-1 identified oriens lacunosum-moleculare predominantly targeted pyramidal neurons, avoiding FS-INs. Overall, our results provide framework translate into discrete subtypes capture diverse specializations -INs.

Language: Английский

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Inhibitory specificity from a connectomic census of mouse visual cortex

Nature, Journal Year: 2025, Volume and Issue: 640(8058), P. 448 - 458

Published: April 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.

Language: Английский

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Connectomics of predicted Sst transcriptomic types in mouse visual cortex

Nature, Journal Year: 2025, Volume and Issue: 640(8058), P. 497 - 505

Published: April 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.

Language: Английский

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Cortical representations of affective pain shape empathic fear in male mice

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 24, 2025

Affect sharing, the ability to vicariously feel others' emotions, constitutes primary component of empathy. However, neural basis for encoding distress and representing shared affective experiences remains poorly understood. Here, using miniature endoscopic calcium imaging, we identify distinct dynamic ensembles in anterior cingulate cortex (ACC) that encode observational fear across both excitatory inhibitory neurons male mice. Notably, discover population dynamics vicarious freezing information are conserved ACC pyramidal specifically represented by affective, rather than sensory, responses direct pain experience. Furthermore, circuit-specific imaging optogenetic manipulations, demonstrate populations projecting periaqueductal gray (PAG), but not basolateral amygdala (BLA), selectively convey regulate fear. Taken together, our findings highlight critical role representations shaping empathic through pain. The affect sharing is fully authors show stably recruits fear,

Language: Английский

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Neocortical somatostatin neuron diversity in cognition and learning

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Lateral inhibition in V1 controls neural and perceptual contrast sensitivity

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Language: Английский

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Making Ramón y Cajal proud: Development of cell identity and diversity in the cerebral cortex

Neuron, Journal Year: 2024, Volume and Issue: 112(13), P. 2091 - 2111

Published: May 15, 2024

Language: Английский

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An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

SUMMARY In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools access manipulate fine subtypes are still limited. Here, performed systematic analysis single cell genomic data identify enhancer candidates for each cortical interneuron subtypes. We established set enhancer-AAV that highly specific distinct populations striatal cholinergic neurons. These enhancers, used in context different effectors, target (fluorescent proteins), observe activity (GCaMP) (opto- or chemo-genetics) also validated our across species. Thus, provide field with powerful study neural circuits functions develop precise targeted therapy.

Language: Английский

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