# Inhibitory and Disinhibitory VIP Interneuron-Mediated Circuits in Neocortex

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $628,919

## Abstract

Summary
GABAergic inhibitory interneurons (INs) are a diverse group of neurons with critical roles in sculpting the
spatiotemporal aspects of circuit activity and signal processing in the cerebral cortex. Moreover, malfunction of
these neurons has been implicated in a number of diseases ranging from epilepsy to schizophrenia, anxiety
disorders and autism. This project is focused on the GABAergic INs that express the neuropeptide vasoactive
intestinal peptide (VIP). VIP INs are the main IN population in the superficial layers of the cortex, and were
recently found to be major targets of cotico-cortical and thalamocortical projections, as well as cholinergic
projections, that mediate top-down or contextual sensory processing and to mainly target inhibitory somatostatin
(SST) INs. Based on this connectivity and the analysis of their patterns of in vivo activity in multiple types of
sensory cortices, these studies have suggested that VIP INs mediate a disinhibitory canonical circuit that is
important in brain state-dependent control of cortical function. VIP INs have been implicated in arousal, attention,
sensory processing and synaptic plasticity and learning. Furthermore, several studies have implicated VIP INs
in schizophrenia and in the cognitive deficits associated with childhood epilepsy. Recent work shows that VIP
INs are diverse. We show they consist of at least three distinct populations with different laminar distribution, as
well as different morphology and potentially different afferent and efferent connectivity, suggesting distinct
inhibitory and disinhibitory actions on pyramidal neurons. The data implies that to discover the circuit
mechanisms by which VIP INs regulate specific cortical functions and the mechanisms by which they cause
disease it is necessary to understand the differential connectivity and function of VIP IN subtypes. This
application uses state-of-the-art electrophysiological and optogenetic methods as well as innovative
intersectional genetic strategies to identify and manipulate specific VIP IN subtypes to understand their efferent
(Aim 1) and afferent connectivity (Aim 2). In Aim 3 we use 2-photon Ca2+ imaging, optogenetic and
pharmacogenetic manipulations in awake behaving mice to discover how VIP IN subtypes regulate the effects
of arousal on cortical functional reorganization and sensory processing. These studies will advance our
understanding of VIP IN function and the mechanisms of top down modulation of sensory processing.

## Key facts

- **NIH application ID:** 10892899
- **Project number:** 5R01NS133751-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Bernardo Rudy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $628,919
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892899

## Citation

> US National Institutes of Health, RePORTER application 10892899, Inhibitory and Disinhibitory VIP Interneuron-Mediated Circuits in Neocortex (5R01NS133751-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10892899. Licensed CC0.

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