# Adolescence, motivation and the maturation of the prefrontal cortex.

> **NIH NIH R01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2022 · $516,451

## Abstract

The aim of the current proposal is to test the hypothesis that signaling through 5-HT1A
receptors in the medial prefrontal cortex during adolescence is important for establishing
lifelong motivation. Prior work suggests that disruption of the serotonin system during
early post-natal development in animal models results in altered anxiety and mood
related behaviors in the full-grown adult animal. One receptor that is particularly relevant
in this regard is the 5-HT1A receptor. Recent data from our lab suggests that loss of
serotonin signaling through 5-HT1A receptors in the medial prefrontal cortex during
adolescence but not during adulthood, results in decreased motivation related behavioral
setpoints. We hypothesize that this is true for both appetitive and avoidance motivation.
The current proposal both examines mechanisms through which altered serotonin
signaling through 5-HT1A receptors in adolescence leads to changes in motivation and
further elucidates the specific nature of the reinforcement related behavior that is
affected. In addition to a loss of function, we will use a biased 5-HT1A agonist as a gain
of function approach bi-directionally modulate 5-HT1A signaling Using slice physiology,
we will assess whether 5-HT1A expressing neurons alter their intrinsic properties as a
result of the disrupted 5-HT1A mediated signaling, or whether there are compensatory
changes in circuit properties resulting from the disruption. Using fiber photometry, we
will determine how the medial prefrontal cortex engages with other circuit nodes like the
dorsal raphe nucleus in tasks that tax motivational systems, with the goal of
understanding the circuit basis for the disrupted behavior. Finally, we will directly
assess whether the sensitivity of mPFC pyramidal neurons to inputs during adolescence
is the critical factor in establishing later motivation. We will do this by manipulating
mPFC principal neuron activity during the sensitive period in adolescence using
DREADDS. Understanding how mPFC plasticity in adolescence can be harnessed to
modulate motivation is a potentially promising strategy for addressing disorder that
emerge in adolescence and often include a prominent motivational component.
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## Key facts

- **NIH application ID:** 10338182
- **Project number:** 5R01MH123153-03
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Eduardo David Leonardo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $516,451
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10338182

## Citation

> US National Institutes of Health, RePORTER application 10338182, Adolescence, motivation and the maturation of the prefrontal cortex. (5R01MH123153-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10338182. Licensed CC0.

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