# Implications of Prefrontal Cortex Development for Adolescent Reward Seeking Behavior

> **NIH NIH K99** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $112,528

## Abstract

PROJECT SUMMARY
As we get older, we learn to modulate our behaviors to optimize reward outcomes. These adaptive choices are
orchestrated by current sensory conditions, internal cognitive states, and future expectations. In adolescence,
rewards circuits that link peripheral detection of sensory stimuli to central circuits involved in decision-making
and motivational states continue to grow, remodeling the microcircuit connectivity within the medial prefrontal
cortex (mPFC). This development may explain why adolescents demonstrate increased impulsivity and
diminished behavioral flexibility, and fail to optimize reward outcomes. However, the developmental changes
within the reward circuits that inform differences in reward learning during adolescence are poorly understood.
The mPFC is a key area for emotional regulation, decision making, and reward-seeking. The reward-
modulating properties of mPFC are derived from inputs from the ventral tegmental area (VTA). During
adolescence, VTA inputs into mPFC are still developing, and the functional impact of these developmental
changes is unknown. One influential theory suggests that increased dopaminergic (DA) signaling in
adolescence drives heightened reward sensitivity. However, additional mechanisms such as changes in local
mPFC connectivity and changes in reward information sent to the mPFC are likely at play. In this proposal, we
use a combination of chemogenetics, optogenetics, anatomical, and neural calcium imaging, to test how the
developing adolescent mPFC (Aim 1) and VTA projections to mPFC (Aim 2) contribute to adolescent reward
behaviors and influence reward optimization strategies (Aim 3). This work reframes the role of neuronal
subtypes, and probes if their role in a given behavior is shaped by the age of the microcircuit, asking the
question, do cells carry the same information in adolescents as they do in adulthood? In addition to the value
of this work from a basic science perspective, this study is likely to produce testable hypotheses that will tackle
why certain psychiatric disorders such as impulse control and feeding disorders tend to emerge during
adolescence. Training in calcium imaging, neuronal activity data analysis and advanced anatomical techniques
will be provided by the mentor Dr. Conor Liston, with additional expertise in 2-photon imaging provided by the
consultants Drs. Rajasethupathy and De Marco Garcia. Dr. Sullivan will serve as a consultant on
developmental behavioral neuroscience, providing feedback on experimental design and outcomes. Dr. Bravo
Rivera will provide an additional behavioral neuroscientific perspective and will be instrumental in providing
additional career development training to the applicant. Together the mentor and the External Advisory
Committee will facilitate the transition of Dr. Manzano Nieves into an independent research career focused on
uncovering how postnatal development alters brain circuits to bias behavior and create psychiatric
vulnerab...

## Key facts

- **NIH application ID:** 10893568
- **Project number:** 5K99MH132082-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Gabriela Manzano Nieves
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $112,528
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893568

## Citation

> US National Institutes of Health, RePORTER application 10893568, Implications of Prefrontal Cortex Development for Adolescent Reward Seeking Behavior (5K99MH132082-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10893568. Licensed CC0.

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