# Organization of Prefrontal Feedback Circuits

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2020 · $514,424

## Abstract

The prefrontal cortex receives information from many brain regions, and captures the essence of events to
extract rules for action. In an uncertain environment opportunities and dangers must also be weighed in
context for flexible behavior, in functions that engage the medial prefrontal cortex (mPFC), the hippocampus
and the amygdala. The roles of these structures in motivated behavior appear to be distinct and often
opposing. The goal of the proposed studies is to investigate the hitherto unknown circuit mechanisms of this
functionally significant network in a non-human primate animal model. The overarching hypothesis is that the
hippocampus, amygdala and mPFC form a tightly linked network whose nodes differentially interface with
excitatory and distinct types of inhibitory neurons, in patterns suited for weighing stimuli in context for adaptive
behavior. Experiments are designed to test this hypothesis by: (1) study of interconnections of the
hippocampus and amygdala and their synaptic circuits with excitatory and inhibitory neurons; (2) study of
pathways from the subgenual mPFC, and hippocampus to the amygdala, which may help balance network
activity via inhibitory mechanisms; (3) investigating if the limbic thalamic reuniens nucleus is a common link for
the amygdala, hippocampus and subgenual mPFC, which may mediate their respective roles in vigilance,
separation of memories, and behavioral context; and (4) testing if synaptic arrangements in limbic thalamic
nuclei from hippocampal, amygdalar and subgenual mPFC pathways are organized like sensory pathways in
the main thalamic relay nuclei. Hypotheses about pathway interactions are based on a theoretical framework
on the organization of the cortex and thalamus, and principles of excitatory and inhibitory control in primates.
Multiple neural pathways will be labeled with tracers, combined with multiple labeling of distinct classes of
inhibitory neurons. Brain tissue will be processed to study pathway features at the level of the light, confocal,
and electron microscope. Quantitative analyses on pathway features will be conducted from the system to the
synapse. Circuits will be modeled to infer their complex normal interactions and perturbation in psychiatric
diseases. Findings from these studies will provide the circuit basis for the role of mPFC, hippocampus and
amygdala in excitatory and inhibitory control for flexible behavior and disruption in anxiety disorders.

## Key facts

- **NIH application ID:** 9900588
- **Project number:** 5R01MH057414-20
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Helen Barbas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $514,424
- **Award type:** 5
- **Project period:** 1999-04-10 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900588

## Citation

> US National Institutes of Health, RePORTER application 9900588, Organization of Prefrontal Feedback Circuits (5R01MH057414-20). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9900588. Licensed CC0.

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