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Serotonin modulation of the development of neural circuits underlying reward processing and impulsivity in adolescents

Award Number: R01MH126178
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 goal of this proposal for the Biobehavioral Research Awards for Innovative New Scientists (BRAINS) program is to understand typical and atypical adolescent development of reward processing and impulsive behavior. These complex phenotypes are found in many psychiatric disorders including attention deficit hyperactivity disorder, borderline personality disorder, and schizophrenia. Adolescence is a sensitive period for the emergence of dysregulated reward processing and disordered impulsivity, and for the development of underlying neural circuits thought to be responsible. However, it is unclear what factors push development towards pathological trajectories and it is unknown how pathology is encoded by changes in neural circuits. The Adolescent Brain Cognitive Development (ABCD) longitudinal study of human brain and behavior is underway to identify factors in adolescence that predict impulsivity and other reward-related phenotypes. Similar longitudinal data from mice are necessary to allow molecular, cellular, and circuit-level interrogation of adolescent development. This knowledge is critical for targeted interventions to alter and prevent developmental pathology. This proposal develops a framework for mouse ABCD studies. We use an innovative approach to measure complex behavioral phenotypes in the homecage that allows for testing on a timescale compatible with assessing the dynamic changes during adolescence. This proposal focuses on the role of serotonin modulation of corticostriatal projections in driving adolescent maturation of reward processing and impulsivity. Using transgenic mouse lines for cell-type and time period-specific manipulations, we will investigate circuit-level mechanisms of serotonin modulation of adolescent developmental trajectories. The high-risk, high-reward use of in vivo calcium imaging in adolescents will uncover the single cell and ensemble- level changes occurring in the adolescent brain that supports adolescent behavioral maturation. Using microendoscope technology we will identify neural changes at the cellular level throughout adolescence, and define a trajectory of pathological development. These studies will point to a timeframe and mechanism for targeted prevention and treatment of developmental pathology related to reward processing and impulsivity. Our results will inform refinement of pharmacotherapies aimed at modulating serotonin signaling in adolescents for the treatment of depression, anxiety, and obsessive compulsive disorder. This research project is highly appropriate for BRAINS funding because it directly addresses two key objectives in the NIMH Strategic Plan and applies novel methods and techniques to advance our understanding of the major conceptual question of what drives adolescent maturation. As an early career investigator, funding for this ambitious proposal, which I’m uniquely equipped to carry out, would allow me to launch an innovative basic research program aimed at understanding the atypical development of reward processing and impulsivity.


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 = $497,323 )
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	4	1/17/2024	NON-COMPETING CONTINUATION	$497,323
														Subtotal = $497,323

Issue Date FY: 2023 ( Subtotal = $555,302 )
2023	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	3	1/19/2023	NON-COMPETING CONTINUATION	$555,302
														Subtotal = $555,302

Issue Date FY: 2022 ( Subtotal = $604,173 )
2022	2022	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	001	2	6/21/2022	NON-COMPETING CONTINUATION	$60,418
2022	2022	TRUSTEES OF DARTMOUTH COLLEGE	6001 PARKHURST HALL STE 207	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	2	2/9/2022	NON-COMPETING CONTINUATION	$543,755
														Subtotal = $604,173

Issue Date FY: 2021 ( Subtotal = $568,974 )
2021	2021	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Mental Health Research Grants	000	1	4/1/2021	NEW	$568,974
														Subtotal = $568,974

Grand Total All Awards = $2,225,772

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Serotonin modulation of the development of neural circuits underlying reward processing and impulsivity in adolescents

Award Number: R01MH126178

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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