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Cell Type Specific Control of Neuronal Signaling

Award Number: F31MH091921
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2010
PERIOD OF PERFORMANCE END DATE: 05/12/2013

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Cell Type Specific Control of Neuronal Signaling - 6. PROJECT SUMMARY / ABSTRACT Dysfunctional neuronal circuits are thought to be responsible for neuropsychiatric disorders, including obsessive-compulsive disorder, Parkinson¿s disease and addiction. G protein-coupled receptors (GPCRs) differentially modulate the activity of neuronal circuits by interacting with different G proteins, (e.g. G-alpha-s, G-alpha-i, and G-alpha-q-families), and these receptors are well-established drug targets. Distinct subpopulations of neurons comprising these circuits often express similar receptor subtypes, making it impossible to create drugs that selectively target receptors in specific circuits. In order to determine how receptors might modulate neuronal circuits, it is necessary to selectively activate GPCR signaling in a specific neuronal population in vivo. For the past two decades, efforts have been made to create tools to selectively manipulate GPCR signaling in distinct neuron populations - from small molecule ligands to genetic deletion - but these approaches have off-target effects. These off-target effects effectively eliminate the possibility to determine how GPCR signaling in a specific neuronal population affects circuitry function. A promising advancement to enable this specific manipulation is the development of the Designer Receptors Exclusively Activated by Designer Drug (DREADD) family of receptors. The objective of this proposal is to validate this recently created tool in vivo using a transgenic mouse expressing the G-alpha-s DREADD in a specific population of neurons in the striatum. Specific Aim 1 will validate the tool by determining whether the G-alpha-s DREADD activates canonical G-alpha-s signaling pathways by measuring cAMP accumulation, ERK1/2 phosphorylation, DARPP-32 phosphorylation, and c-Fos expression. Specific Aim 2 will validate the physiological relevance of the G-alpha-s DREADD-induced signaling by assessing its effects on animal behavior. The completion of this proposal will provide neuroscientists a powerful new tool to exclusively modulate GPCR signaling in specific neuronal populations.


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: 2017 ( Subtotal = -$289 )
2017	2012	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health National Research Service Awards for Research Training	000	3	5/15/2017	NON-COMPETING CONTINUATION	-$289
														Subtotal = -$289

Issue Date FY: 2013 ( Subtotal = -$3,800 )
2013	2012	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health National Research Service Awards for Research Training	000	3	8/30/2013	NON-COMPETING CONTINUATION	-$3,800
														Subtotal = -$3,800

Issue Date FY: 2012 ( Subtotal = $30,920 )
2012	2012	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health National Research Service Awards for Research Training	000	3	6/6/2012	NON-COMPETING CONTINUATION	$30,920
														Subtotal = $30,920

Issue Date FY: 2011 ( Subtotal = $30,488 )
2011	2011	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health National Research Service Awards for Research Training	000	2	8/18/2011	NON-COMPETING CONTINUATION	$30,488
														Subtotal = $30,488

Issue Date FY: 2010 ( Subtotal = $29,932 )
2010	2010	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health National Research Service Awards for Research Training	000	1	6/16/2010	NEW	$29,932
2010	2010	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	440 WEST FRANKLIN ST, CB #1350	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health National Research Service Awards for Research Training	001	1	6/16/2010	NEW	$0
														Subtotal = $29,932

Grand Total All Awards = $87,251

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Cell Type Specific Control of Neuronal Signaling

Award Number: F31MH091921

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2010

PERIOD OF PERFORMANCE END DATE: 05/12/2013

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