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Actions of proline at receptors and synapses

Award Number: R21MH130678
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Actions of proline at receptors and synapses - Disturbances in brain handling of the amino acid proline are linked to a wide variety neurological and behavioral disorders including schizophrenia, autism, epilepsy, intellectual disability, and depression. Although proline has been suggested to be a candidate neurotransmitter, a demonstration of a prolinergic component of synaptic has been lacking. Proline is thought to mediate its action, in part, via activation of ionotropic glutamate receptors, which mediate the majority of synaptic transmission in the central nervous system. Yet, the actions of proline at glutamate receptors and synaptic transmission are not well understood. We hypothesize that the proline sensitivity of ionotropic glutamate receptors varies with subunit composition. Moreover, we propose that prolinergic transmission can be demonstrated by pharmacologically probing transmission between neurons that express SLC6A7, the high-affinity proline transporter responsible for a majority of synaptic proline uptake, and its postsynaptic partners. We will use a combination of electrophysiological, molecular, immunocytochemical, and imaging methods we will examine: 1) the pharmacological profile of proline at recombinant ionotropic glutamate receptors with distinct subunit compositions; 2) the preferred hippocampal cell types that are targets of putative prolinergic neurons; and 3) the how synaptically evoked proline accumulations shape glutamatergic transmission. Collectively, these studies will fill in major gaps in our knowledge regarding the actions of proline at glutamate receptors and synapses where prolinergic transmission likely occurs.


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 = -$17,577 )
2026	2023	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Mental Health Research Grants	000	2	1/5/2026	NON-COMPETING CONTINUATION	-$17,577
														Subtotal = -$17,577

Issue Date FY: 2023 ( Subtotal = $231,000 )
2023	2023	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Mental Health Research Grants	000	2	7/14/2023	NON-COMPETING CONTINUATION	$231,000
														Subtotal = $231,000

Issue Date FY: 2022 ( Subtotal = $192,500 )
2022	2022	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Mental Health Research Grants	000	1	7/20/2022	NEW	$192,500
														Subtotal = $192,500

Grand Total All Awards = $405,923

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Actions of proline at receptors and synapses

Award Number: R21MH130678

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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