# Adolescent plasticity of the dopaminergic mesofrontal circuit: cellular mechanisms and behavioral roles

> **NIH NIH F32** · UNIVERSITY OF ROCHESTER · 2021 · $70,494

## Abstract

Recent evidence suggests that many psychiatric disorders such as schizophrenia are developmental
disorders characterized by complex alterations in neuronal circuits. Dopamine has long been recognized as a
key player in psychiatric illness and many current therapeutic strategies for psychosis target the dopaminergic
system. While many of these therapeutics effectively target delusions and hallucinations in patients, no effective
therapies exist to manage the cognitive symptoms of illnesses such as schizophrenia. Research in both patients
and animal models indicates that mesofrontal dopaminergic circuit abnormalities are involved in cognitive deficits
in psychiatric illnesses. Prior work in our lab has identified a unique adolescent activity-dependent plasticity in
the mesofrontal dopaminergic projections that is lacking in adult animals. However, the mechanisms behind this
adolescent plasticity process remain unclear. Previous work and preliminary experiments in our lab demonstrate
that ventral tegmental area activity elicits both presynaptic axonal bouton outgrowth and postsynaptic cortical
neuronal activity. In Aim 1 I will further characterize the response of cortical excitatory and inhibitory neurons to
mesofrontal activity and determine if cortical postsynaptic activity is necessary for mesofrontal presynaptic
plasticity through opto/chemogenetic silencing of postsynaptic excitatory and inhibitory neurons. Microglia, the
innate immune cells of the central nervous system, have also been identified as key participants in neuronal
plasticity, development, and neurodevelopmental disorders. In Aim 2 I will determine if microglia respond to
changes in dopaminergic activity and if microglia mediate mesofrontal dopaminergic plasticity. Finally, to
elucidate the unknown role that mesofrontal neural activity plays in normal development, in Aim 3 I will perturb
mesofrontal activity chemogenetically during adolescence and evaluate the impact on both frontal cortical activity
and frontal cortical dependent behaviors. The results obtained from these complementary, but independent aims
will provide key insights into adolescent dopaminergic system development. With an improved understanding of
mesofrontal circuit development and function, new pathways for therapeutic intervention can be identified and
tested in the context of neurodevelopmental psychiatric diseases.

## Key facts

- **NIH application ID:** 10228964
- **Project number:** 1F32MH124298-01A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Rianne Stowell
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,494
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228964

## Citation

> US National Institutes of Health, RePORTER application 10228964, Adolescent plasticity of the dopaminergic mesofrontal circuit: cellular mechanisms and behavioral roles (1F32MH124298-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10228964. Licensed CC0.

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