# Core C

> **NIH NIH P50** · JOHNS HOPKINS UNIVERSITY · 2020 · $122,837

## Abstract

Research under the current proposal is designed to determine behavioral alterations relevant to schizophrenia
(SZ), which is elicited by activation of stress-associated cascades and the E-I imbalance in the prefrontal
cortex in mouse models that carry microtubule-associated genetic variants. We will also study how adolescent
social isolation exacerbates these changes at the molecular, circuitry, and behavioral levels in collaboration
with three Projects. In addition to performing basic behavioral characterization of the mouse models, this Core
will conduct behavioral assessments for neurocognitive domains that are mediated by medial prefrontal cortex
and orbitofrontal cortex, such as behavioral flexibility, including outcome expectancy in goal directed behavior,
and working memory. Our rationale for use of specific behavioral assessments aimed at prefrontal systems is
grounded in research that 1) documents the critical role of prefrontal cortex (PFC) circuitry in the information
encoding mechanisms required to support behavioral performance in these paradigms across rodent and
primate species, 2) implicates PFC systems supporting these functions in SZ by anatomical and
physiological/neuroimaging evidence from patients, 3) demonstrates a vulnerability of such PFC-mediated
behaviors/networks to stress exposure, including underlying mechanisms in PFC. Importantly, the
assessments hold potential for the study of species-conserved cognitive mechanisms in the human brain to
provide translational opportunities based on this preclinical research program. As such, the work in Core C is
consistent with the Research Domain Criteria (RDoC) approach for advancing a biological understanding of the
pathophysiology of major psychiatric illness and creating a platform for discovery of new therapeutics. Core C
will consult with the investigators of the Projects both for conducting basic behavioral assays, for implementing
behavioral experiments with a focus on analytically powerful protocols targeting PFC-mediated behaviors, and
will lead data analysis and interpretation of findings in behavioral studies under the research program. In
addition to its scientific value to the immediate objectives of the research program, the work of this Core may
have broader translational significance in the neuropsychiatric field. As the molecular pathways under
investigation are better understood in the context of behavioral profiling, the work of the core could identify
assessments that are best suited to target dysfunctional mechanisms in animal models of SZ. In this way the
proposed behavioral research may yield innovative findings of more general preclinical importance.

## Key facts

- **NIH application ID:** 9978146
- **Project number:** 5P50MH094268-10
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Michela Gallagher
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $122,837
- **Award type:** 5
- **Project period:** 2011-07-12 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978146

## Citation

> US National Institutes of Health, RePORTER application 9978146, Core C (5P50MH094268-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9978146. Licensed CC0.

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