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Presynaptic modulation of synaptic inhibition onto hippocampal pyramidal neurons

Award Number: R56NS140423
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Presynaptic modulation of synaptic inhibition onto hippocampal pyramidal neurons - PROJECT SUMMARY Throughout the hippocampus, pyramidal cells integrate excitatory and inhibitory inputs from a diverse population of interneurons. These cells provide feedforward and feedback inhibition onto CA1 pyramidal cells, and can be recruited via glutamate spillover, a phenomenon that describes non-synaptic actions of glutamate diffusing away from the synaptic cleft. The prevailing view, at present, is that glutamate spillover leads to activation of presynaptic group III metabotropic (mGluRIII) glutamate receptors, which inhibit synaptic excitation and inhibition only onto interneurons, not CA1 pyramidal cells. Against this interpretation, our preliminary data indicates that spillover activation of mGluRIII receptors also exists at inhibitory synapses formed onto CA1 pyramidal cells, when experiments are performed under experimental conditions that mimic more closely the ionic composition of the cerebrospinal fluid. The main goals in this application are: (i) to determine how mGluRIII activation via glutamate spillover varies between excitatory and inhibitory inputs, and among inhibitory inputs formed by different classes of interneurons; (ii) to identify the intracellular signaling mechanisms that couple mGluRIII activation to neurotransmitter release; (iii) the determine the sub-cellular location of different type of mGluRIII receptors at different types of inhibitory synapses onto CA1 pyramidal cells; (iv) to determine how mGluRIII activation alters encoding of spatial information by hippocampal CA1 place cells in vivo. The proposed experiments capitalize on in vitro and in vivo electrophysiology, and EM approaches. These findings will generate new information on the operating principles of neuronal circuits involved in spatial map representation and will contribute to the future development of effective strategies to treat disease states associated with hippocampal neural circuit dysfunction, like epilepsy and autism spectrum disorder.


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: 2026 ( Subtotal = $0 )
2026	2025	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	1400 WASHINGTON AVE	ALBANY	NY	12222	ALBANY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/4/2026	NEW	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $565,257 )
2025	2025	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	1400 WASHINGTON AVE	ALBANY	NY	12222	ALBANY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/7/2025	NEW	$565,257
														Subtotal = $565,257

Grand Total All Awards = $565,257

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Presynaptic modulation of synaptic inhibition onto hippocampal pyramidal neurons

Award Number: R56NS140423

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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