# Afferent Regulation of Prefrontal Maturation during Adolescence

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $399,750

## Abstract

Abstract
Adolescence is a vulnerable period of postnatal development for the onset of major psychiatric disorders where
the prefrontal cortex (PFC) is involved. According to the NIMH Council's Workgroup Report, many psychiatric
disorders can only be understood as an interaction between brain development and susceptibility to risk
factors. Although many progresses have been made in the field during the past few years, a comprehensive
understanding of the cellular and circuit level mechanisms regulating the developmental trajectory of neural
processes involved in these disorders remains incomplete. Thus, our long-term goal is to identify sensitive
developmental processes during adolescence that contribute to the onset of psychiatric disorders where the
PFC is compromised. From studies performed during the preceding grant period, we have found that a
hallmark of PFC maturation during adolescence is the functional re-calibration of an excitatory-inhibitory (E-I)
balance state. In addition to the gain of GABA function, there is a facilitation of GluN2B and GluN2A NMDAR
transmission in the PFC that is intimately linked to ventral hippocampal and basolateral amygdalar inputs. Yet,
the extent to which coordinated activation of ventral hippocampal and basolateral amygdalar inputs during
adolescence are required for the functional maturation of the PFC remains unclear. We will fill this gap in
knowledge through the pursuit of 3 Specific Aims. We will use an input-specific chemogenetic strategy to
transiently inhibit PFC afferent transmission at 3 non-overlapping adolescent periods to establish the exact
window(s) of susceptibility for the gain/functional maturation of the GABA and NMDA synaptic components of
the PFC E-I balance and their impact on PFC-dependent behaviors in adulthood. Together, the proposed aims
are expected to uncover key neural circuit processes that contribute to the enhanced PFC vulnerability during
adolescence to developmental insults. Such knowledge is expected to provide insights on the implementation
of new therapeutic interventions to prevent/mitigate the incidence of cognitive and affective deficits often seen
in mental illnesses that emerge during adolescence.

## Key facts

- **NIH application ID:** 10844635
- **Project number:** 5R01MH086507-13
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Kuei-Yuan Tseng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,750
- **Award type:** 5
- **Project period:** 2010-07-08 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844635

## Citation

> US National Institutes of Health, RePORTER application 10844635, Afferent Regulation of Prefrontal Maturation during Adolescence (5R01MH086507-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10844635. Licensed CC0.

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