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Complex genetic encoding of experience by NPAS4 resulting in a sophisticated reorganization of inhibition.

Award Number: F31MH124355
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/01/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2023

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Complex genetic encoding of experience by NPAS4 resulting in a sophisticated reorganization of inhibition. - Project Abstract When a mouse explores an enriched environment the pyramidal neurons in the CA1 region of its hippocampus receive excitatory inputs and fire action potentials to encode information about their complex environment. This experience-induced activity results in the expression of the activity dependent transcription factor NPAS4 via de novo transcription and translation, as well as local dendritic translation of preexisting NPAS4 mRNA. This enriched environment induced NPAS4 produces changes in gene expression resulting in a sophisticated reorganization of inhibition across the somato-dendritic axis, with an increase in the number CCK Basket Cell synapses onto the somatic region and a decrease in the number of inhibitory synapses on the radiatum dendrites of NPAS4 expressing cells. This proposal describes experiments designed to determine 1) the genetic identity of the radiatum targeting interneuron type which loses synapses onto NPAS4 expressing cells, and 2) the necessity of dendritic translation of NPAS4 in this sophisticated reorganization. These experiments will provide insight into fundamental biology underlying the complex regulation of inhibitory networks and the role that experience and activity dependent dendritic translation play in this process. Given the known relationships between dysregulation of inhibition, dendritic translation, and a variety of neurological disorders with experience dependent symptomology, this work will aid our understanding of neurological function and dysfunction.


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: 2024 ( Subtotal = -$5,000 )
2024	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	3	9/23/2024	NON-COMPETING CONTINUATION	-$5,000
														Subtotal = -$5,000

Issue Date FY: 2023 ( Subtotal = $44,998 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	3	11/22/2022	NON-COMPETING CONTINUATION	$44,056
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	001	3	3/6/2023	NON-COMPETING CONTINUATION	$942
														Subtotal = $44,998

Issue Date FY: 2022 ( Subtotal = $43,074 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	001	2	7/5/2022	NON-COMPETING CONTINUATION	$716
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	2	11/26/2021	NON-COMPETING CONTINUATION	$42,358
														Subtotal = $43,074

Issue Date FY: 2021 ( Subtotal = $41,465 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	001	1	11/23/2020	NEW	$0
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	000	1	11/23/2020	NEW	$38,449
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	003	1	8/11/2021	SUPPLEMENT FOR EXPANSION	$2,500
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Mental Health Research Grants	002	1	3/12/2021	NEW	$516
														Subtotal = $41,465

Grand Total All Awards = $124,537

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Complex genetic encoding of experience by NPAS4 resulting in a sophisticated reorganization of inhibition.

Award Number: F31MH124355

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/01/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2023

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