Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Response-dependent dynamics of cell-specific inhibition in cortical networks in vivo.

ABSTRACT: In the visual cortex, inhibitory neurons alter the computations performed by target cells via combination of two fundamental operations, division and subtraction. The origins of these operations have been variously ascribed to differences in neuron classes, synapse location or receptor conductances. Here, by utilizing specific visual stimuli and single optogenetic probe pulses, we show that the function of parvalbumin-expressing and somatostatin-expressing neurons in mice in vivo is governed by the overlap of response timing between these neurons and their targets. In particular, somatostatin-expressing neurons respond at longer latencies to small visual stimuli compared with their target neurons and provide subtractive inhibition. With large visual stimuli, however, they respond at short latencies coincident with their target cells and switch to provide divisive inhibition. These results indicate that inhibition mediated by these neurons is a dynamic property of cortical circuits rather than an immutable property of neuronal classes.

SUBMITTER: El-Boustani S

PROVIDER: S-EPMC4268659 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Calcium dynamics of cortical astrocytic networks in vivo.

Project description:Large and long-lasting cytosolic calcium surges in astrocytes have been described in cultured cells and acute slice preparations. The mechanisms that give rise to these calcium events have been extensively studied in vitro. However, their existence and functions in the intact brain are unknown. We have topically applied Fluo-4 AM on the cerebral cortex of anesthetized rats, and imaged cytosolic calcium fluctuation in astrocyte populations of superficial cortical layers in vivo, using two-photon laser scanning microscopy. Spontaneous [Ca(2+)](i) events in individual astrocytes were similar to those observed in vitro. Coordination of [Ca(2+)](i) events among astrocytes was indicated by the broad cross-correlograms. Increased neuronal discharge was associated with increased astrocytic [Ca(2+)](i) activity in individual cells and a robust coordination of [Ca(2+)](i) signals in neighboring astrocytes. These findings indicate potential neuron-glia communication in the intact brain.

| S-EPMC387267 | biostudies-literature

Massively parallel <i>in vivo</i> Perturb-seq reveals cell type-specific transcriptional networks in cortical development.

Project description:Systematic analysis of gene function across diverse cell types in vivo is hindered by two challenges: obtaining sufficient cells from live tissues and accurately identifying each cell's perturbation in high-throughput single-cell assays. Leveraging AAV's versatile cell type tropism and high labeling capacity, we expanded the resolution and scale of in vivo CRISPR screens: allowing phenotypic analysis at single-cell resolution across a multitude of cell types in the embryonic brain, adult brain, and peripheral nervous system. We undertook extensive tests of 86 AAV serotypes, combined with a transposon system, to substantially amplify labeling and accelerate in vivo gene delivery from weeks to days. Using this platform, we performed an in utero genetic screen as proof-of-principle and identified pleiotropic regulatory networks of Foxg1 in cortical development, including Layer 6 corticothalamic neurons where it tightly controls distinct networks essential for cell fate specification. Notably, our platform can label >6% of cerebral cells, surpassing the current state-of-the-art efficacy at <0.1% (mediated by lentivirus), and achieve analysis of over 30,000 cells in one experiment, thus enabling massively parallel in vivo Perturb-seq. Compatible with various perturbation techniques (CRISPRa/i) and phenotypic measurements (single-cell or spatial multi-omics), our platform presents a flexible, modular approach to interrogate gene function across diverse cell types in vivo, connecting gene variants to their causal functions.

| S-EPMC10542124 | biostudies-literature

Inhibition increases response variability and reduces stimulus discrimination in random networks of cortical neurons.

Project description:Much of what is known about the contribution of inhibition to stimulus discrimination is due to extensively studied sensory systems, which are highly structured neural circuits. The effect of inhibition on stimulus representation in less structured networks is not as clear. Here we exercise a biosynthetic approach in order to study the impacts of inhibition on stimulus representation in non-specialized network anatomy. Combining pharmacological manipulation, multisite electrical stimulation and recording from ex-vivo randomly rewired networks of cortical neurons, we quantified the effects of inhibition on response variability and stimulus discrimination at the population and single unit levels. We find that blocking inhibition quenches variability of responses evoked by repeated stimuli and enhances discrimination between stimuli that invade the network from different spatial loci. Enhanced stimulus discrimination is reserved for representation schemes that are based on temporal relation between spikes emitted in groups of neurons. Our data indicate that - under intact inhibition - the response to a given stimulus is a noisy version of the response evoked in the absence of inhibition. Spatial analysis suggests that the dispersion effect of inhibition is due to disruption of an otherwise coherent, wave-like propagation of activity.

| S-EPMC6428807 | biostudies-literature

Massively parallel in vivo Perturb-seq reveals cell type-specific transcriptional networks in cortical development

Project description:Leveraging AAV's versatile tropism and labeling capacity, we expanded the scale of in vivo CRISPR screen with single-cell transcriptomic phenotyping across embryonic to adult brains and peripheral nervous systems. Through extensive tests of 86 AAV serotypes, combined with transposon systems, we substantially amplified labeling and accelerated in vivo gene delivery from weeks to days. Our proof-of-principle in utero screen identified the pleiotropic effects of Foxg1, highlighting its tight regulation of distinct networks essential for cell fate specification of Layer 6 corticothalamic neurons. Notably, our platform can label >6% of cerebral cells, surpassing the current state-of-the-art efficacy at <0.1% by lentivirus, to achieve analysis of over 30,000 cells in one experiment and enable massively parallel in vivo Perturb-seq. Compatible with various phenotypic measurements (single-cell or spatial multi-omics), it presents a flexible approach to interrogate gene function across cell types in vivo, translating gene variants to their causal function.

2023-12-05 | GSE249416 | GEO

Cortical depth-dependent temporal dynamics of the BOLD response in the human brain.

Project description:Recent animal studies at high field have shown that blood oxygen level-dependent (BOLD) contrast can be specific to the laminar vascular architecture of the cortex, by differences in its temporal dynamics in reference to cortical depth. In this study, we characterize the temporal dynamics of the hemodynamic response (HDR) across cortical depth in the human primary motor and visual cortex, at 7?T and using very short stimuli and with high spatial and temporal resolution. We find that the shape and temporal dynamics of the HDR changed in an orderly manner across cortical depth. Compared with the pial vasculature, HDRs in deeper gray matter are significantly faster in onset time (by ?0.5?second) and peak time (?2?seconds), and are narrower (by ?1?second) and with smaller amplitude, in line with the known vascular organization across cortical depth and the transit of deoxygenated blood through the vasculature. The width of the HDR in deeper gray matter was as short as 2.1?seconds, indicating that neurovascular coupling takes place at a shorter timescale than previously reported in the human brain. These findings open the possibility to probe layer-specific hemodynamics and neurovascular coupling mechanisms in human gray matter.

| S-EPMC3208150 | biostudies-literature

Locomotion-dependent remapping of distributed cortical networks.

Project description:The interactions between neocortical areas are fluid and state-dependent, but how individual neurons couple to cortex-wide network dynamics remains poorly understood. We correlated the spiking of neurons in primary visual (V1) and retrosplenial (RSP) cortex to activity across dorsal cortex, recorded simultaneously by widefield calcium imaging. Neurons were correlated with distinct and reproducible patterns of activity across the cortical surface; while some fired predominantly with their local area, others coupled to activity in distal areas. The extent of distal coupling was predicted by how strongly neurons correlated with the local network. Changes in brain state triggered by locomotion strengthened affiliations of V1 neurons with higher visual and motor areas, while strengthening distal affiliations of RSP neurons with sensory cortices. Thus, the diverse coupling of individual neurons to cortex-wide activity patterns is restructured by running in an area-specific manner, resulting in a shift in the mode of cortical processing during locomotion.

| S-EPMC6701985 | biostudies-literature

Multiscale model of primary motor cortex circuits predicts in vivo cell-type-specific, behavioral state-dependent dynamics.

Project description:Understanding cortical function requires studying multiple scales: molecular, cellular, circuit, and behavioral. We develop a multiscale, biophysically detailed model of mouse primary motor cortex (M1) with over 10,000 neurons and 30 million synapses. Neuron types, densities, spatial distributions, morphologies, biophysics, connectivity, and dendritic synapse locations are constrained by experimental data. The model includes long-range inputs from seven thalamic and cortical regions and noradrenergic inputs. Connectivity depends on cell class and cortical depth at sublaminar resolution. The model accurately predicts in vivo layer- and cell-type-specific responses (firing rates and LFP) associated with behavioral states (quiet wakefulness and movement) and experimental manipulations (noradrenaline receptor blockade and thalamus inactivation). We generate mechanistic hypotheses underlying the observed activity and analyzed low-dimensional population latent dynamics. This quantitative theoretical framework can be used to integrate and interpret M1 experimental data and sheds light on the cell-type-specific multiscale dynamics associated with several experimental conditions and behaviors.

| S-EPMC10592234 | biostudies-literature

Inhibition stabilization is a widespread property of cortical networks.

Project description:Many cortical network models use recurrent coupling strong enough to require inhibition for stabilization. Yet it has been experimentally unclear whether inhibition-stabilized network (ISN) models describe cortical function well across areas and states. Here, we test several ISN predictions, including the counterintuitive (paradoxical) suppression of inhibitory firing in response to optogenetic inhibitory stimulation. We find clear evidence for ISN operation in mouse visual, somatosensory, and motor cortex. Simple two-population ISN models describe the data well and let us quantify coupling strength. Although some models predict a non-ISN to ISN transition with increasingly strong sensory stimuli, we find ISN effects without sensory stimulation and even during light anesthesia. Additionally, average paradoxical effects result only with transgenic, not viral, opsin expression in parvalbumin (PV)-positive neurons; theory and expression data show this is consistent with ISN operation. Taken together, these results show strong coupling and inhibition stabilization are common features of the cortex.

| S-EPMC7324160 | biostudies-literature

Antiepileptic drugs induce subcritical dynamics in human cortical networks.

Project description:Cortical network functioning critically depends on finely tuned interactions to afford neuronal activity propagation over long distances while avoiding runaway excitation. This importance is highlighted by the pathological consequences and impaired performance resulting from aberrant network excitability in psychiatric and neurological diseases, such as epilepsy. Theory and experiment suggest that the control of activity propagation by network interactions can be adequately described by a branching process. This hypothesis is partially supported by strong evidence for balanced spatiotemporal dynamics observed in the cerebral cortex; however, evidence of a causal relationship between network interactions and cortex activity, as predicted by a branching process, is missing in humans. Here this cause-effect relationship is tested by monitoring cortex activity under systematic pharmacological reduction of cortical network interactions with antiepileptic drugs. This study reports that cortical activity cascades, presented by the propagating patterns of epileptic spikes, as well as temporal correlations decline precisely as predicted for a branching process. The results provide a missing link to the branching process theory of cortical network function with implications for understanding the foundations of cortical excitability and its monitoring in conditions like epilepsy.

| S-EPMC7245074 | biostudies-literature

Cortical layer-specific critical dynamics triggering perception.

Project description:Perceptual experiences may arise from neuronal activity patterns in mammalian neocortex. We probed mouse neocortex during visual discrimination using a red-shifted channelrhodopsin (ChRmine, discovered through structure-guided genome mining) alongside multiplexed multiphoton-holography (MultiSLM), achieving control of individually specified neurons spanning large cortical volumes with millisecond precision. Stimulating a critical number of stimulus-orientation-selective neurons drove widespread recruitment of functionally related neurons, a process enhanced by (but not requiring) orientation-discrimination task learning. Optogenetic targeting of orientation-selective ensembles elicited correct behavioral discrimination. Cortical layer-specific dynamics were apparent, as emergent neuronal activity asymmetrically propagated from layer 2/3 to layer 5, and smaller layer 5 ensembles were as effective as larger layer 2/3 ensembles in eliciting orientation discrimination behavior. Population dynamics emerging after optogenetic stimulation both correctly predicted behavior and resembled natural internal representations of visual stimuli at cellular resolution over volumes of cortex.

| S-EPMC6711485 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data