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Mechanisms of Stress-Enhanced Aversive Conditioning

Award Number: R01MH078064
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Mechanisms of Stress-Enhanced Aversive Conditioning - ABSTRACT Cognitive dysfunction, including the inappropriate generalization (i.e., overgeneralization) of negative episodic memories, is a core diagnostic criterion of major depression, and is recognized as a key determinant of severe affective symptoms. For this reason, we believe that studying the neurobiology of memory generalization could have considerable translational impact for depression. We propose to identify the cellular and circuit mechanisms subserving generalization of negative context (episodic-like) memories using a newly developed paradigm of stress-induced generalization (SIG). Aim 1 will rely on most recent approaches that allow us to visualize and manipulate neuronal populations coding either specific and general features of context memories. Through these techniques, we expect to determine whether stress promotes or disrupts the reactivation of these neuronal populations during memory retrieval. Aim 2 will utilize chemogenetic and optogenetic approaches, alone or in combination with neuronal labeling, to determine whether excitatory ventral tegmental area (VTA) to dorsal hippocampus (DH) projections, which signal negative valence, contribute to SIG. Inhibition of these projections is expected to reduce generalization, especially in females. Aim 3 will focus on the role of MS to DH projections, which we suspect play a more prominent role in SIG in males than in females. In addition to the approaches used in Aim 2, we will determine the effects of stress and cholinergic neuromodulation on hippocampal oscillations and acetylcholine release, and we will explore the stress-mediated changes of global brain activity using manganese-enhanced magnetic resonance imaging. Upon competition of this project, we expect to have identified the main cellular and circuit (mal)adaptations induced by stress that result in lasting generalization of negative context memories. Approaches that prove effective in reversing SIG could be the foundation for novel treatments of cognitive deficits associated with depression and affective disorders.


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: 2025 ( Subtotal = $583,412 )
2025	2025	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	000	20	1/24/2025	NON-COMPETING CONTINUATION	$583,412
														Subtotal = $583,412

Issue Date FY: 2024 ( Subtotal = $686,366 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	000	19	1/24/2024	NON-COMPETING CONTINUATION	$617,729
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	001	19	8/14/2024	NON-COMPETING CONTINUATION	$68,637
														Subtotal = $686,366

Issue Date FY: 2023 ( Subtotal = $617,729 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	000	18	1/31/2023	NON-COMPETING CONTINUATION	$617,729
														Subtotal = $617,729

Issue Date FY: 2022 ( Subtotal = $652,048 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	002	17	1/21/2022	NON-COMPETING CONTINUATION	$586,843
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	003	17	5/10/2022	NON-COMPETING CONTINUATION	$65,205
2022	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	000	16	10/27/2021	COMPETING CONTINUATION	$24,920
2022	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	001	15	10/27/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$24,920
														Subtotal = $652,048

Issue Date FY: 2021 ( Subtotal = $711,927 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	002	16	3/25/2021	COMPETING CONTINUATION	$640,229
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	003	16	5/5/2021	COMPETING CONTINUATION	$71,137
2021	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	001	15	12/21/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$235,789
2021	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	004	14	8/31/2021	NON-COMPETING CONTINUATION	-$24,920
2021	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	14	12/21/2020	NON-COMPETING CONTINUATION	-$235,228
2021	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Mental Health Research Grants	005	15	8/31/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$24,920
														Subtotal = $711,927

Issue Date FY: 2020 ( Subtotal = $374,527 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	14	3/18/2020	NON-COMPETING CONTINUATION	$374,527
														Subtotal = $374,527

Issue Date FY: 2019 ( Subtotal = $374,527 )
2019	2019	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	13	3/18/2019	NON-COMPETING CONTINUATION	$374,527
														Subtotal = $374,527

Issue Date FY: 2018 ( Subtotal = $374,527 )
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	001	12	6/4/2018	NON-COMPETING CONTINUATION	$37,453
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	12	3/6/2018	NON-COMPETING CONTINUATION	$337,074
														Subtotal = $374,527

Issue Date FY: 2017 ( Subtotal = $493,924 )
2017	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	11	3/7/2017	NON-COMPETING CONTINUATION	$444,532
2017	2017	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	001	11	7/29/2017	NON-COMPETING CONTINUATION	$49,392
														Subtotal = $493,924

Issue Date FY: 2016 ( Subtotal = $492,504 )
2016	2016	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	001	10	3/24/2016	COMPETING CONTINUATION	$492,504
2016	2015	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60201	COOK	USA	Mental Health Research Grants	000	9	3/19/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $492,504

Issue Date FY: 2015 ( Subtotal = $381,250 )
2015	2015	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	9	4/3/2015	NON-COMPETING CONTINUATION	$381,250
														Subtotal = $381,250

Issue Date FY: 2014 ( Subtotal = $381,250 )
2014	2014	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	8	5/9/2014	NON-COMPETING CONTINUATION	$381,250
														Subtotal = $381,250

Issue Date FY: 2013 ( Subtotal = $366,000 )
2013	2013	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	7	5/8/2013	NON-COMPETING CONTINUATION	$366,000
														Subtotal = $366,000

Issue Date FY: 2012 ( Subtotal = $381,250 )
2012	2012	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	6	4/5/2012	NON-COMPETING CONTINUATION	$381,250
														Subtotal = $381,250

Issue Date FY: 2011 ( Subtotal = $381,250 )
2011	2011	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	001	5	6/17/2011	COMPETING CONTINUATION	$381,250
2011	2010	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60201	COOK	USA	Mental Health Research Grants	000	4	6/15/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $381,250

Issue Date FY: 2010 ( Subtotal = $237,825 )
2010	2010	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	4	6/10/2010	NON-COMPETING CONTINUATION	$237,825
														Subtotal = $237,825

Issue Date FY: 2009 ( Subtotal = $237,825 )
2009	2009	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Mental Health Research Grants	000	3	7/1/2009	NON-COMPETING CONTINUATION	$237,825
														Subtotal = $237,825

Issue Date FY: 2008 ( Subtotal = $237,825 )
2008	2008	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60201	COOK	USA	Mental Health Research Grants	000	2	6/4/2008	NON-COMPETING CONTINUATION	$237,825
														Subtotal = $237,825

Issue Date FY: 2007 ( Subtotal = $237,825 ) (Continued on the next page)
Grand Total All Awards = $8,203,791

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Mechanisms of Stress-Enhanced Aversive Conditioning

Award Number: R01MH078064

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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