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Investigating how signaling via adhesion GPCR Latrophilins regulates synapse formation and specificity in the hippocampus

Award Number: R00MH117235
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY: Brain functions require the assembly and maintenance of distinct synaptic subtypes into stereotyped neural circuits. However, the fundamental cellular and molecular mechanisms underlying input-specific synapse formation in neural circuits remain poorly understood. Our studies during the K99 phase revealed an important role of the adhesion GPCR Latrophilins (Lphns) in hippocampal excitatory synaptic specificity. We recently found using rescue experiments that the role of Lphn2/3 in hippocampal input-specific excitatory synapse formation requires G-protein and/or u-Arrestin coupling. In parallel studies, we found that compartmentalized postsynaptic cAMP signaling is a prominent driver of excitatory synapse formation. Efforts during the R00 phase at Vanderbilt University will be focused on examining the G-protein and u-Arrestin intracellular signaling mechanisms of Lphns and other adhesion GPCRs at synapses in the mammalian central nervous system. Furthermore, we will determine the functions of unstudied adhesion GPCRs in neural circuits, and define the extracellular ligands of orphan adhesion GPCRs in the brain. We will develop novel molecular tools including viral-mediated nanobody targeting of signaling modulators to probe the roles of compartmentalized synaptic signaling pathways in input-specific excitatory, inhibitory and neuromodulatory synapse formation in neural circuits. We will also develop novel live super-resolution STORM and confocal imaging techniques to image synapse formation, maintenance and elimination in real-time. We expect these studies to reveal fundamental principles of how neural circuits are established by diverse synapses in the mammalian central nervous system, and elucidate the functions and signaling mechanisms of the understudied adhesion GPCRs in the brain.


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 = $239,616 )
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	5	1/16/2023	NON-COMPETING CONTINUATION	$239,616
														Subtotal = $239,616

Issue Date FY: 2022 ( Subtotal = $244,378 )
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	001	4	5/10/2022	NON-COMPETING CONTINUATION	$24,439
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	4	1/4/2022	NON-COMPETING CONTINUATION	$219,939
														Subtotal = $244,378

Issue Date FY: 2021 ( Subtotal = $249,000 )
2021	2021	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	3	2/17/2021	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $732,994

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Investigating how signaling via adhesion GPCR Latrophilins regulates synapse formation and specificity in the hippocampus

Award Number: R00MH117235

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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