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Kainate receptor signaling in striatal synaptic function and plasticity

Award Number: F31MH099807
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/01/2013
PERIOD OF PERFORMANCE END DATE: 02/28/2016

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Kainate receptor signaling in striatal synaptic function and plasticity - DESCRIPTION (provided by applicant): Obsessive Compulsive Disorder (OCD) is a chronic anxiety disorder characterized by maladaptive compulsive behavior such as excessive grooming, hoarding or checking. OCD is a debilitating disease, estimated to affect 1-2% of the population, making it the fourth most common mental illness after depression, alcoholism and social anxiety disorder. Despite innovations in pharmacological, behavioral, and surgical treatments at least 30% of cases prove intractable. Recent advances in understanding the neurobiological underpinnings of OCD have highlighted a central role for dysfunction of the glutamate system, the brain's major excitatory neurotransmitter, in the subcortical region of the striatum. In addition to clinical literature linking OCD to alterations in striatal activity, anima studies have indicated that the synapses formed by cortical neurons onto striatal spiny projection neurons (SPNs) are crucial in regulating habit formation. This convergent evidence indicates that perturbations in normal striatal activity will be crucial to understanding the emergence of maladaptive compulsive, habitual behavior seen in patients with OCD. Mice lacking expression of the kainate receptor, a subtype of glutamate receptor, have a dramatic compulsive grooming and anxiety phenotype reminiscent of that seen in OCD. Despite being highly expressed in the striatum, it is not known how kainate receptors contribute to striatal synaptic transmission and plasticity, and therefore to the overall regulation of the striatal circut. Preliminary work has determined that, in the striatum, activating kainate receptors facilitates the release of endocannabinoids. This is a novel interaction that has not been previously demonstrated. Endocannabinoids are common neuromodulators that serve to down-regulate transmitter release at synapses throughout the brain. I hypothesize that this coupling of kainate receptors to endocannabinoids provides a physiologically relevant method of regulating glutamate release in the striatum that is highly important for the behavioral phenotype of kainate receptor knockout mice. The following aims propose to determine the biochemical mechanism by which kainate receptors couple to endocannabinoids and the contribution of this interaction to normal striatal synaptic function and plasticity.


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: 2019 ( Subtotal = -$655 )
2019	2015	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	3	9/24/2019	NON-COMPETING CONTINUATION	-$655
														Subtotal = -$655

Issue Date FY: 2017 ( Subtotal = -$9,420 )
2017	2015	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	3	1/30/2017	NON-COMPETING CONTINUATION	-$9,420
														Subtotal = -$9,420

Issue Date FY: 2015 ( Subtotal = $43,120 )
2015	2015	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	3	2/18/2015	NON-COMPETING CONTINUATION	$43,120
														Subtotal = $43,120

Issue Date FY: 2014 ( Subtotal = $42,676 )
2014	2014	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health National Research Service Awards for Research Training	000	2	3/3/2014	NON-COMPETING CONTINUATION	$42,676
														Subtotal = $42,676

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2012	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60201	COOK	USA	Mental Health National Research Service Awards for Research Training	000	1	9/23/2013	NEW	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $42,232 )
2012	2012	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60201	COOK	USA	Mental Health National Research Service Awards for Research Training	001	1	9/14/2012	NEW	$0
2012	2012	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health National Research Service Awards for Research Training	000	1	9/14/2012	NEW	$42,232
														Subtotal = $42,232

Grand Total All Awards = $117,953

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Kainate receptor signaling in striatal synaptic function and plasticity

Award Number: F31MH099807

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/01/2013

PERIOD OF PERFORMANCE END DATE: 02/28/2016

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