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The role of VTA neurotransmitter co-release in health and disease

Award Number: F32MH122192
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2022

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The role of VTA neurotransmitter co-release in health and disease - PROJECT SUMMARY Elucidating the neural circuit mechanisms underlying both homeostatic and uncontrolled motivation are crucial for developing better therapeutic treatments for neuropsychiatric disorders like depression or bipolar disorder. As part of mesolimbic brain reward circuitry, the ventral tegmental area (VTA) is generally reduced to its dopamine projection neurons. However, VTA also contains neurons that co-release inhibitory GABA and excitatory glutamate that are capable of powerfully modulating motivation. However, the functional role of this GABA/glutamate co-release in health and disease is not well understood. Why would these neurons simultaneously send both a `stop' and `go' signal? This set of proposed experiments will systematically test the hypothesis that VTA GABA/glutamate co- release serves as a mechanism to normalize postsynaptic activity in a homeostatic manner. Using optogenetics to drive VTA GABA/glutamate co-release in downstream structures that regulate mood and motivation, I will use chemogenetic approaches and chronic behavioral manipulations that alter postsynaptic activity, and then test the physiological and behavioral effect of optogenetically driving VTA GABA/glutamate co-release. These experiments will reveal basic mechanisms of neurotransmitter co-release and uncover their role within mesolimbic circuitry in modulating the switch between reward and aversion. The proposed experiments will also provide the investigator with extensive training in cell-attached and whole-cell patch clamp electrophysiology, and mouse genetics. Showing a brain mechanism capable of normalizing activity and in turn motivation can provide a novel target for treating neuropsychiatric diseases, as well as elucidate the mysterious role of neurotransmitter co- release beyond neuropsychiatric disease.


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: 2023 ( Subtotal = -$24 )
2023	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	3	6/20/2023	NON-COMPETING CONTINUATION	-$24
														Subtotal = -$24

Issue Date FY: 2022 ( Subtotal = $50,514 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	002	3	12/21/2021	NON-COMPETING CONTINUATION	$68,562
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	004	3	7/18/2022	NON-COMPETING CONTINUATION	$6
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	005	3	7/29/2022	NON-COMPETING CONTINUATION	-$19,288
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	003	3	4/29/2022	NON-COMPETING CONTINUATION	$1,234
2022	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	001	2	12/20/2021	NON-COMPETING CONTINUATION	$0
2022	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	1	12/17/2021	NEW	$0
														Subtotal = $50,514

Issue Date FY: 2021 ( Subtotal = $66,390 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	001	2	2/5/2021	NON-COMPETING CONTINUATION	$1,080
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	2	12/11/2020	NON-COMPETING CONTINUATION	$65,310
														Subtotal = $66,390

Issue Date FY: 2019 ( Subtotal = $61,226 )
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	1	9/6/2019	NEW	$61,226
														Subtotal = $61,226

Grand Total All Awards = $178,106

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The role of VTA neurotransmitter co-release in health and disease

Award Number: F32MH122192

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2022

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