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

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2021 · $568,974

## Abstract

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 u...

## Key facts

- **NIH application ID:** 10200242
- **Project number:** 1R01MH126178-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Katherine M Nautiyal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $568,974
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200242

## Citation

> US National Institutes of Health, RePORTER application 10200242, Serotonin modulation of the development of neural circuits underlying reward processing and impulsivity in adolescents (1R01MH126178-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10200242. Licensed CC0.

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