Friday, November 22, 2024 11/22/2024

Regulation of Intrinsic Plasticity in Neural Circuits

Award Number: R01MH067284
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 The public health and economic impact of chronic sleep deprivation (SD) have grown enormously with the increasingly global and 24-hour nature of our society. The human costs are also high; SD is an exacerbating factor in many mental illnesses. In spite of this, however, we know very little about the mechanisms by which SD alters memory circuits. Memory formation is bidirectionally sensitive to sleep levels. SD has negative effects on its formation, while learning has been shown to enhance sleep drive, suggesting that there are circuit interactions binding memory and sleep centers. In Drosophila, we have a very detailed understanding both of the computations that underlie memory formation and the structure of sleep circuits. This proposal leverages this knowledge to understand, for the first time at a circuit and molecular level, how SD dysregulates both short-term and long-term memory formation. In Aim 1 we investigate the effects of sleep deprivation on short-term memory formation. Based on preliminary data, we hypothesize that SD-dependent changes in dopamine dynamics degrade coincidence detection. We test specific circuit and molecular mechanisms and propose strategies to ameliorate SD pathology. In Aim 2 we probe the effect of SD on protein synthesis-dependent long-term memory. Preliminary data demonstrate that pre-training SD blocks activity-dependent local protein synthesis and that local synthesis is sensitive to inhibition of MAPK pathways. We will uncover the molecular mechanisms of how spaced training promotes this critical step in initiation of stable memory formation and we will determine how SD disrupts the process. Looking at SD through a lens of plasticity dysfunction will provide a strong molecular understanding of how memory formation is adversely affected by lack of sleep. Importantly, these studies also will deepen our knowledge of how memory is formed in well-rested brains and give us insight into what parts of the process are vulnerable to disruption, making this work relevant to understanding a wide range of other pathologies.


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 = $625,922 )
2024	2024	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	21	5/9/2024	COMPETING CONTINUATION	$625,922
2024	2023	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	20	5/9/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $625,922

Issue Date FY: 2023 ( Subtotal = $406,250 )
2023	2023	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	20	12/21/2022	NON-COMPETING CONTINUATION	$365,625
2023	2023	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	20	3/10/2023	NON-COMPETING CONTINUATION	$40,625
														Subtotal = $406,250

Issue Date FY: 2022 ( Subtotal = $406,251 )
2022	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	19	5/10/2022	NON-COMPETING CONTINUATION	$40,625
2022	2022	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	19	10/26/2021	NON-COMPETING CONTINUATION	$365,625
2022	2018	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	002	15	9/26/2022	NON-COMPETING CONTINUATION	$1
														Subtotal = $406,251

Issue Date FY: 2021 ( Subtotal = $406,250 )
2021	2021	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	18	4/7/2021	NON-COMPETING CONTINUATION	$40,625
2021	2021	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	18	11/6/2020	NON-COMPETING CONTINUATION	$365,625
														Subtotal = $406,250

Issue Date FY: 2020 ( Subtotal = $406,250 )
2020	2020	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	17	2/3/2020	NON-COMPETING CONTINUATION	$40,625
2020	2020	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	17	11/13/2019	NON-COMPETING CONTINUATION	$365,625
														Subtotal = $406,250

Issue Date FY: 2019 ( Subtotal = $541,370 )
2019	2019	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	16	11/6/2018	COMPETING CONTINUATION	$385,750
2019	2019	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	003	16	6/12/2019	SUPPLEMENT FOR EXPANSION	$155,620
2019	2019	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	002	16	3/25/2019	COMPETING CONTINUATION	$60,627
2019	2018	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	15	3/25/2019	NON-COMPETING CONTINUATION	-$60,627
														Subtotal = $541,370

Issue Date FY: 2018 ( Subtotal = $406,250 )
2018	2018	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	15	11/10/2017	NON-COMPETING CONTINUATION	$365,625
2018	2018	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	15	6/1/2018	NON-COMPETING CONTINUATION	$40,625
														Subtotal = $406,250

Issue Date FY: 2017 ( Subtotal = $406,250 )
2017	2017	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	14	11/10/2016	NON-COMPETING CONTINUATION	$365,625
2017	2017	BRANDEIS UNIVERSITY	415 SOUTH ST	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	14	5/9/2017	NON-COMPETING CONTINUATION	$40,625
														Subtotal = $406,250

Issue Date FY: 2016 ( Subtotal = $406,250 )
2016	2016	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02254		USA	Mental Health Research Grants	001	13	3/12/2016	NON-COMPETING CONTINUATION	$40,625
2016	2016	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02254		USA	Mental Health Research Grants	000	13	11/6/2015	NON-COMPETING CONTINUATION	$365,625
														Subtotal = $406,250

Issue Date FY: 2015 ( Subtotal = $405,521 )
2015	2015	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02254		USA	Mental Health Research Grants	000	12	11/14/2014	NON-COMPETING CONTINUATION	$364,968
2015	2015	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02254		USA	Mental Health Research Grants	001	12	1/9/2015	NON-COMPETING CONTINUATION	$40,553
														Subtotal = $405,521

Issue Date FY: 2014 ( Subtotal = $404,271 )
2014	2014	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02254		USA	Mental Health Research Grants	000	11	11/25/2013	COMPETING CONTINUATION	$404,271
														Subtotal = $404,271

Issue Date FY: 2013 ( Subtotal = $375,408 )
2013	2013	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	10	6/18/2013	NON-COMPETING CONTINUATION	$23,463
2013	2013	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	10	11/5/2012	NON-COMPETING CONTINUATION	$351,945
														Subtotal = $375,408

Issue Date FY: 2012 ( Subtotal = $391,050 )
2012	2012	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	9	11/21/2011	NON-COMPETING CONTINUATION	$351,945
2012	2012	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	9	3/15/2012	NON-COMPETING CONTINUATION	$39,105
														Subtotal = $391,050

Issue Date FY: 2011 ( Subtotal = $391,050 )
2011	2011	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	8	5/24/2011	NON-COMPETING CONTINUATION	$35,550
2011	2011	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	8	11/10/2010	NON-COMPETING CONTINUATION	$355,500
														Subtotal = $391,050

Issue Date FY: 2010 ( Subtotal = $395,000 )
2010	2010	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	7	2/1/2010	NON-COMPETING CONTINUATION	$39,500
2010	2010	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	000	7	11/27/2009	NON-COMPETING CONTINUATION	$355,500
														Subtotal = $395,000

Issue Date FY: 2009 ( Subtotal = $387,800 ) (Continued on the next page)
2009	2009	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	002	6	4/9/2009	COMPETING CONTINUATION	$38,780
2009	2009	BRANDEIS UNIVERSITY	415 SO ST, 119 BERNSTEIN-MARCU	WALTHAM	MA	02453	MIDDLESEX	USA	Mental Health Research Grants	001	6	12/5/2008	COMPETING CONTINUATION	$349,020
Grand Total All Awards = $8,227,429

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Regulation of Intrinsic Plasticity in Neural Circuits

Award Number: R01MH067284

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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