# The effect of adolescent thalamic inhibition on adult prefrontal cortical function

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $51,036

## Abstract

PROJECT SUMMARY/ABSTRACT
 The prefrontal cortex (PFC) plays a crucial role in cognitive behaviors that are disrupted in many, if not
all, psychiatric disorders. It is also responsible for integrating a number of subcortical excitatory inputs, including
from the mediodorsal nucleus of the thalamus (MD) and the basolateral amygdala (BLA). These inputs are also
implicated in many PFC-dependent behaviors and symptoms of these psychiatric disorders. For instance,
connectivity between the MD and the PFC is essential for working memory, but is disrupted in patients with
schizophrenia. Notably, this hypoconnectivity is also found in adolescents with a clinical high risk for
schizophrenia, serving as a predictor of later illness conversion, which may indicate an important role for these
circuits in the development of the disorder.
 Adolescence is a vulnerable time window in the progression of psychiatric disorders, and it is also a
period of maturation of PFC circuitry. Therefore, during this period, the brain may be more susceptible to external
signals, and transient perturbations can result in persistent changes in circuitry. In sensory cortex (e.g., visual
system), there are “sensitive periods” when transient disruption of one excitatory input (e.g., one eye) leads to
rewiring of thalamocortical connections as well as sensory impairments (e.g., amblyopia) that persist even after
the input has been restored. This proposal aims to discover if there is a competitive, activity-dependent
sensitive period during adolescence that governs the maturation of medial PFC (mPFC) circuits in mice,
similar to what has been described in other cortical regions.
 This question will be tested using a combination of transgenic mouse models, viral inhibitory DREADD
constructs, behavioral tests, viral tracers for anatomical studies, and slice electrophysiology. Aim 1 will discover
whether there is indeed a sensitive period in adolescence or adulthood during which transient inhibition of the
MD will have persistent consequences on behaviors that are dependent both on MD-mPFC circuitry and BLA-
mPFC circuitry. Aim 2 will use anatomical labeling and in vitro slice electrophysiology to discover whether
transient MD inhibition can persistently disrupt the densities and strengths of excitatory projections to the mPFC.
 These studies will discover mechanisms that govern the development of inputs into the mPFC, and may
also be instructive for understanding the circuit how a developmental imbalance in activity between different
subcortical inputs can increase risk for developing a psychiatric disorder.

## Key facts

- **NIH application ID:** 10196997
- **Project number:** 5F31MH119691-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Laura Jacqueline Benoit
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10196997

## Citation

> US National Institutes of Health, RePORTER application 10196997, The effect of adolescent thalamic inhibition on adult prefrontal cortical function (5F31MH119691-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10196997. Licensed CC0.

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