# Gating of Information Flow Within the Nucleus Accumbens

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $705,367

## Abstract

Stress and the resultant anxiety can provide motivation and prevent reckless behavior. However, when
experience in excess can be deleterious. This is particularly true when stressors occur during the peripubertal
period, when the brain is undergoing substantial plastic changes. In addition, there are significant male/female
differences in experience with stress. Thus, our studies in rats show that, although males and females show
similar impacts of peripubertal stress immediately after the stress, early stress preferentially impacts
cognitive/salience processes in males as adults and postpubertal stress impacting affective behaviors in females
as adults. Our preliminary results suggest that both male and female rats exposed to neurodevelopmental stress
show parvalbumin (PV) neuron loss in the ventral hippocampus (vHipp) leading to a hyperdopaminergic state,
this occurs via different pathways and different periods within puberty depending on sex. Thus, prepubertal
(PreP) stress in males but not females leads to parvalbumin (PV) neuron loss in the basolateral amygdala (BLA)
and mesoassociative striatal dopamine hyperactivity, whereas postpubertal (PostP) stress in females but not
males leads to hyperactivity in the reuniens (RE) nucleus of the thalamus and medial mesolimbic dopamine
overdrive. We propose that this difference is due to a differential impact of medial prefrontal cortical (mPFC)
regulation, with infralimbic PFC (ilPFC) controlling RE activity and prelimbic PFC (plPFC) impacting the BLA.
Thus, our preliminary data suggest that stress has timing- and sex-specific impacts that elicit distinct pathologies
via different circuits in the adult. Our overarching hypothesis is that PreP stress causes males to be selectively
vulnerable to VTA-associative striatal DA hyperactivity in the adult via precocious maturation of the plPFC-
BLA pathway and loss of BLA PV interneurons. In contrast, PostP stress causes selective activation of the
RE, potentially via PV loss in the reticular thalamic nucleus innervated by the ilPFC, in females leading to
hyperactivation of the mesolimbic DA system in adults. We will examine this along three specific aims: 1)
Examine how PreP vs PostP stress impacts the BLA-vHipp projection in male and female rats. 2) Examine how
PreP vs PostP stress impacts the RE-vHipp projection in male and female rats, and 3) Examine how the plPFC
and ilPFC regulate BLA-vHIpp and RE-vHipp response to PreP and PostP stress. This will give substantial insight
into how early stress leads to circuit-wide disruptions that render an individual more susceptible to pathological
states as adults.

## Key facts

- **NIH application ID:** 10800075
- **Project number:** 2R01MH057440-26A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** ANTHONY A GRACE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $705,367
- **Award type:** 2
- **Project period:** 1997-08-15 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10800075

## Citation

> US National Institutes of Health, RePORTER application 10800075, Gating of Information Flow Within the Nucleus Accumbens (2R01MH057440-26A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10800075. Licensed CC0.

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