# GABAergic expression in MPFC-amygdala pathway of adults with autism or psychosis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $199,375

## Abstract

ABSTRACT
The prefrontal cortex and amygdala are strongly and consistently implicated in most
behaviorally-defined neurodevelopmental disorders, including the autism (ASD) and psychosis
spectrum disorders, such as schizophrenia (SCZ). Although ASD and SCZ do differ in some
core symptomatology, they share common neurobiological, genetic, and behavioral features –
chiefly socioemotional impairments and anxiety. We hypothesize that the medial prefrontal
cortex (mPFC) and amygdala, key neural circuitry that regulates anxiety, will show similar
neuropathological features across the disorders, specifically reduced inhibitory control over the
circuit via the GABAergic system that would normally keep anxiety in check. Widespread
evidence in other brain regions, including the dorsolateral prefrontal cortex (dlPFC), point to
either reductions in the number of GABAergic interneurons and/or transmission of GABA in ASD
and SCZ. However, GABAergic control via the mPFC-amygdala pathway that modulates anxiety
has surprisingly not been examined in either disorder. This key gap in knowledge hinders
development of targeted, neuroscience-driven biotherapeutics. We propose to take the
fundamental first step to determine if alterations in the GABAergic system of mPFC supra- and
infra- granular layers (Specific Aim 1) and amygdala total, lateral, basal, accessory basal, and
central nuclei (Specific Aim 2) in the brains of individuals with ASD and/or SCZ relative to age-
and sex-matched control brains are due to a: i) decrease in the number of GABAergic cells –
defined by presence of glutamate decarboxylase-67—GAD67 (i.e. GAD1), the enzyme required
for GABA synthesis, and/or ii) decrease in GABA production from interneurons to
pyramidal/principal excitatory neurons – measured by GAD67 mRNA transcription levels. In
addition, we hypothesize that a subclass of GABAergic inhibitory neurons that are parvalbumin
positive (PV+) will disproportionately be reduced in mPFC infragranular layers as well as
amygdala lateral and basal nuclei. Lastly, given findings from our previous work, we anticipate
age-related changes in these regions and therefore will limit this study to 36 well-characterized
age- and sex-matched adult brains from our collection. Our findings will serve as a fundamental
reference for which mechanistic studies and animal models of these uniquely human disorders
can be built upon.

## Key facts

- **NIH application ID:** 10527728
- **Project number:** 1R21MH129806-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Cynthia Schumann
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $199,375
- **Award type:** 1
- **Project period:** 2022-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527728

## Citation

> US National Institutes of Health, RePORTER application 10527728, GABAergic expression in MPFC-amygdala pathway of adults with autism or psychosis (1R21MH129806-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10527728. Licensed CC0.

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