# Modeling age-specific computational strategies during reward seeking

> **NIH NIH K99** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $199,800

## Abstract

PROJECT SUMMARY
The neuronal circuitry underlying motivational processes in adolescent models is understudied but clinically
relevant because disorders such as depression, schizophrenia, and substance use disorder, which are marked
by alterations in motivation, emerge during adolescence. The frontal cortex and striatum are critical targets
because they are amongst the last regions to mature. My current work investigated how orbitofrontal cortex
(OFC)-dorsomedial (DMS) circuits control response inhibition in adolescent and adult rats, and the impact of
adolescent alcohol exposure on these networks. I found that adolescent alcohol exposure is associated with
changes in OFC and DMS response to conditioned stimuli and rats' ability to inhibit a response in adulthood. In
alcohol-naive animals, adolescents and adults differed in response to both reward, and actions preceding
rewards in both the OFC and DMS. In a separate study, I recorded from dopamine neurons and observed that
adolescents exhibited a larger phasic response to reward in a stimulus-driven task, while adults exhibit a larger
response when reward is acquired during a goal-driven task. Collectively, these data suggest adolescent
alcohol exposure promotes lasting changes in OFC-DMS circuits, and that adolescents and adults employ
different computational strategies during reward-seeking, likely due to age-specific activity in cortical-striatal
circuits. The proposed projects use a combination of in vivo electrophysiology recordings, computational
modeling and chemogenetics to test the hypotheses that (1) developmental maturation is characterized by an
enhanced ability to employ goal-directed control of behavior and (2) adolescent alcohol exposure causes
pathology in neural circuits required for goal-directed control, thereby leading to risk of addiction-related
behaviors. I will simultaneously record single units and local field potentials in the OFC and DMS in adolescent
and adult rats performing an operant conditioning task (Aim 1). Next, I will integrate experimental and
computational approaches to model neural strategies underlying motivated behavior in adolescents and adults
(Aim 2). During the independent phase, I will use chemogenetics to test the model predictions and determine
causality between behavior and physiology (Aim 3), and determine how engagement of different computational
strategies is impacted by adolescent alcohol exposure and associated with addiction vulnerability (Aim 4).
These translational results will enhance our mechanistic and computational understanding of adolescent brain
function which is fundamental for understanding the etiology and pathophysiology of disorders with an
adolescent onset, such as addiction.

## Key facts

- **NIH application ID:** 10579064
- **Project number:** 1K99AA030670-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Aqilah Maryam McCane
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $199,800
- **Award type:** 1
- **Project period:** 2022-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10579064

## Citation

> US National Institutes of Health, RePORTER application 10579064, Modeling age-specific computational strategies during reward seeking (1K99AA030670-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10579064. Licensed CC0.

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