# Molecular and Cellular Correlates of Plasticity in Hippocampal-Prefrontal Circuitry

> **NIH NIH R01** · LIEBER INSTITUTE, INC. · 2020 · $678,813

## Abstract

The hippocampal-prefrontal circuit is implicated in many neuropsychiatric illnesses. This circuit is critically
involved in multiple aspects of cognition and emotional regulation, and is particularly vulnerable to stress, which
is a key precipitating factor for many of these disorders. Chronic stress can have deleterious effects on neuronal
structure and physiological function in the hippocampus, and impair hippocampal-dependent behavior, including
processing of contextual fear memories. The hippocampus and prefrontal cortex communicate during cognitive
and emotional tasks by altering the coherence of oscillatory activity between the two regions. However, the
cellular and molecular events that drive these changes in hippocampal-prefrontal synchrony, and how they are
influenced by stress, are not well understood. Understanding the mechanisms by which exposure to stress leads
to disruptions in hippocampal-prefrontal interactions during fear regulation is a high priority given that altered
fear-related behavior is prominent in many neuropsychiatric disorders. Our preliminary data support the
hypothesis that exposure to stress impacts plasticity in the hippocampal-prefrontal pathway, leading to disrupted
connectivity between the two regions and enhanced fear-related behavior. Many of the risk factors for
neuropsychiatric disorders, including stress, affect genes that play important roles in the development and
plasticity of synapses. Hence, disruptions in synaptic connections of the long-range projections between the
hippocampus and prefrontal cortex could contribute to impairments in hippocampal-prefrontal synchrony.
However, there is a dearth of research aimed at understanding molecular signaling pathways in these projection
cells. The central hypothesis of this proposal is that defined programs of cellular and molecular signaling in
hippocampal-prefrontal projection neurons control their structure and function, and that these signaling pathways
regulate patterns of neural activity and connectivity between the two structures. The overall goals of this
application are to 1) understand how stress drives molecular and cellular signaling in hippocampal-prefrontal
projection cells to control their physiological function; and 2) determine how plasticity in hippocampal-prefrontal
projections neurons impacts functional connectivity in this circuit to control fear-related behavior. We use a
technically sophisticated combination of neuronal morphology analysis with endoscopic imaging and in vivo
electrophysiology to understand how stress impacts cellular plasticity in hippocampal-prefrontal projection
neurons. We then determine how these cellular correlates of plasticity impact hippocampal-prefrontal synchrony
during fear-related behavior. In addition to cellular correlates, we combine molecular profiling techniques with
retrograde viral approaches to investigate molecular contributions to plasticity in hippocampal-prefrontal
neurons. The research will revea...

## Key facts

- **NIH application ID:** 9972060
- **Project number:** 2R01MH105592-06
- **Recipient organization:** LIEBER INSTITUTE, INC.
- **Principal Investigator:** Keri Martinowich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $678,813
- **Award type:** 2
- **Project period:** 2015-06-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972060

## Citation

> US National Institutes of Health, RePORTER application 9972060, Molecular and Cellular Correlates of Plasticity in Hippocampal-Prefrontal Circuitry (2R01MH105592-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972060. Licensed CC0.

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