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Role of cortical GABAergic interneurons in psychedelic drug action

Award Number: R01MH137047
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/03/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Role of cortical GABAergic interneurons in psychedelic drug action - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $627,945 )
2025	2025	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Mental Health Research Grants	000	2	7/22/2025	NON-COMPETING CONTINUATION	$627,945
														Subtotal = $627,945

Issue Date FY: 2024 ( Subtotal = $627,945 )
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Mental Health Research Grants	000	1	9/3/2024	NEW	$627,945
														Subtotal = $627,945

Grand Total All Awards = $1,255,890

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Role of cortical GABAergic interneurons in psychedelic drug action

Award Number: R01MH137047

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/03/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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