The role of inhibitory circuits in hippocampal memory processing

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(8), P. 476 - 492

Published: May 30, 2022

Language: Английский

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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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Specialized connectivity of molecular layer interneuron subtypes leads to disinhibition and synchronous inhibition of cerebellar Purkinje cells

Neuron, Journal Year: 2024, Volume and Issue: 112(14), P. 2333 - 2348.e6

Published: April 30, 2024

Language: Английский

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Cognitive Impairment Associated with Schizophrenia: From Pathophysiology to Treatment

The Annual Review of Pharmacology and Toxicology, Journal Year: 2022, Volume and Issue: 63(1), P. 119 - 141

Published: Sept. 24, 2022

Cognitive impairment is a core feature of schizophrenia and major contributor to poor functional outcomes. Methods for assessment cognitive dysfunction in are now well established. In addition, there has been increasing appreciation recent years the additional role social driving outcomes contributions sensory-level higher-order impairments. At neurochemical level, acute administration N-methyl-d-aspartate receptor (NMDAR) antagonists reproduces pattern neurocognitive associated with schizophrenia, encouraging development treatments targeted at both NMDAR its interactome. local-circuit an auditory neurophysiological measure, mismatch negativity, emerged as veridical index excitatory/inhibitory imbalance critical biomarker early-stage translational drug development. Although no compounds have yet approved treatment several candidates showing promise early-phase testing.

Language: Английский

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The plasticitome of cortical interneurons

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 24(2), P. 80 - 97

Published: Dec. 30, 2022

Language: Английский

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Ripple-selective GABAergic projection cells in the hippocampus

Neuron, Journal Year: 2022, Volume and Issue: 110(12), P. 1959 - 1977.e9

Published: April 29, 2022

Ripples are brief high-frequency electrographic events with important roles in episodic memory. However, the vivo circuit mechanisms coordinating ripple-related activity among local and distant neuronal ensembles not well understood. Here, we define key characteristics of a long-distance projecting GABAergic cell group mouse hippocampus that selectively exhibits firing during ripples while staying largely silent theta-associated states when most other cells active. The high ripple-associated commenced before ripple onset reached its maximum peak, signature theta-OFF, ripple-ON pattern being preserved across awake sleep states. Controlled by septal GABAergic, cholinergic, CA3 glutamatergic inputs, these ripple-selective innervate parvalbumin cholecystokinin-expressing interneurons also targeting variety extra-hippocampal regions. These results demonstrate existence hippocampal element is uniquely positioned to coordinate dynamics assemblies.

Language: Английский

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Cortex-wide response mode of VIP-expressing inhibitory neurons by reward and punishment

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Nov. 23, 2022

Neocortex is classically divided into distinct areas, each specializing in different function, but all could benefit from reinforcement feedback to inform and update local processing. Yet it remains elusive how global signals like reward punishment are represented cortical computations. Previously, we identified a neuron type, vasoactive intestinal polypeptide (VIP)-expressing interneurons, auditory cortex that recruited by behavioral reinforcers mediates disinhibitory control inhibiting other inhibitory neurons. As the same circuit present virtually throughout cortex, wondered whether VIP neurons likewise cortex. We monitored neural activity dozens of regions using three-dimensional random access two-photon microscopy fiber photometry while mice learned an discrimination task. found during initial learning produce rapid, cortex-wide activation most interneurons. This recruitment mode showed variations temporal dynamics individual across areas. Neither weak sensory tuning interneurons visual nor their arousal state modulation was fully predictive reinforcer responses. suggest response supports cell-type-specific mechanism which organism-level information about regulates processing plasticity.

Language: Английский

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VIP interneuron impairment promotes in vivo circuit dysfunction and autism-related behaviors in Dravet syndrome

Cell Reports, Journal Year: 2023, Volume and Issue: 42(6), P. 112628 - 112628

Published: June 1, 2023

Dravet syndrome (DS) is a severe neurodevelopmental disorder caused by loss-of-function variants in SCN1A, which encodes the voltage-gated sodium channel subunit Nav1.1. We recently showed that neocortical vasoactive intestinal peptide interneurons (VIP-INs) express Nav1.1 and are hypoexcitable DS (Scn1a+/−) mice. Here, we investigate VIP-IN function at circuit behavioral level performing vivo 2-photon calcium imaging awake wild-type (WT) Scn1a+/− pyramidal neuron activation during transition from quiet wakefulness to active running diminished mice, optogenetic of VIP-INs restores activity WT levels locomotion. selective Scn1a deletion reproduces core autism-spectrum-disorder-related behaviors addition cellular- circuit-level deficits function, but without epilepsy, sudden death, or avoidance seen global model. Hence, impaired vivo, may underlie non-seizure cognitive comorbidities DS.

Language: Английский

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Mouse hippocampal CA1 VIP interneurons detect novelty in the environment and support recognition memory

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 114115 - 114115

Published: April 1, 2024

In the CA1 hippocampus, vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) play a prominent role in disinhibitory circuit motifs. However, specific behavioral conditions that lead to disinhibition remain uncertain. To investigate relevance of VIP-IN activity, we employed wireless technologies allowing us monitor and manipulate their function freely behaving mice. Our findings reveal that, during spatial exploration new environments, VIP-INs hippocampal region become highly active, facilitating rapid encoding novel information. Remarkably, both pyramidal neurons (PNs) exhibit increased activity when encountering changes environment, including context- object-related alterations. Concurrently, somatostatin- parvalbumin-expressing inhibitory populations show an inverse relationship with PN revealing occurs on timescale seconds. Thus, VIP-IN-mediated may constitute crucial element novelty acquisition recognition memory.

Language: Английский

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Behavioral strategy shapes activation of the Vip-Sst disinhibitory circuit in visual cortex

Neuron, Journal Year: 2024, Volume and Issue: 112(11), P. 1876 - 1890.e4

Published: March 5, 2024

In complex environments, animals can adopt diverse strategies to find rewards. How distinct differentially engage brain circuits is not well understood. Here, we investigate this question, focusing on the cortical Vip-Sst disinhibitory circuit between vasoactive intestinal peptide-postive (Vip) interneurons and somatostatin-positive (Sst) interneurons. We characterize behavioral used by mice during a visual change detection task. Using dynamic logistic regression model, that individual use mixtures of comparison strategy statistical timing strategy. Separately, also have periods task engagement disengagement. Two-photon calcium imaging shows large strategy-dependent differences in neural activity excitatory, Sst inhibitory, Vip inhibitory cells response both image changes omissions. contrast, has limited effects population activity. diversity correlates be understood parsimoniously as increased activation strategy, which facilitates task-appropriate responses.

Language: Английский

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