# Role of cortical GABAergic interneurons in psychedelic drug action

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $627,945

## Abstract

PROJECT SUMMARY
 Psychedelics are increasingly studied as a potential treatment for mental illnesses. For example, recent
clinical trials showed positive outcomes after psilocybin-assisted psychotherapy for patients with major
depressive disorder. The results are notable because of the durability of the beneficial effects after one or two
dosing sessions, in which significant reduction of symptoms was detectable for at least several weeks and
potentially up to several months. Although the neurobiology responsible for the potential therapeutic effect
remains unclear, it has been suggested that neural plasticity in cortical pyramidal cells may be a contributing
factor. However, pyramidal cells are embedded in cortical microcircuits and interact closely with GABAergic
interneurons. The extent to which major interneuron subtypes may contribute to the psilocybin-induced
changes in neural plasticity and behavior is unknown. The goal of this proposal is to determine the effects of
psilocybin on the three major subtypes of GABAergic interneurons in the mouse medial frontal cortex. In Aim 1,
we will use cell type-specific electrophysiology to measure how each cell type respond in spiking activity to the
administration of psilocybin. In Aim 2, we will determine whether serotonin receptors that are expressed in the
interneurons may be mediating psilocybin’s plasticity-promoting actions. In Aim 3 we will test if manipulating
interneuron activity may alter psilocybin’s effect on stress-related behaviors. These experiments are designed
to provide insights into how the excitatory-inhibitory microcircuit may shape the action of psilocybin in the
neocortex and to identify cell types that are essential for the effects of psilocybin on neural plasticity and
behavior.

## Key facts

- **NIH application ID:** 10941139
- **Project number:** 1R01MH137047-01
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** CHUN-HAY ALEX KWAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $627,945
- **Award type:** 1
- **Project period:** 2024-09-03 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10941139

## Citation

> US National Institutes of Health, RePORTER application 10941139, Role of cortical GABAergic interneurons in psychedelic drug action (1R01MH137047-01). Retrieved via AI Analytics 2026-09-04 from https://api.ai-analytics.org/grant/nih/10941139. Licensed CC0.

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