# Molecular Mechanisms of Memory Consolidation in the Amygdala-Hippocampal Circuit

> **NIH NIH P20** · UNIVERSITY OF MISSISSIPPI MED CTR · 2024 · $252,749

## Abstract

Project Summary
Sleep and memory dysfunction are key features across many psychiatric disorders. Patients with schizophrenia
commonly display both decreased sleep spindles and memory consolidation deficits. In comparison, people
suffering from post-traumatic stress disorder have sleep disruption and nightmares associated with heightened
fear memories. A growing number of studies support the theory that infrequently used dendritic spines are
pruned during sleep, thus improving memories by enhancing the signal to noise ratio of frequently reinforced
synaptic connections. Our published and preliminary data demonstrates that dendritic spines in neurons that
encoded a recent contextual fear memory trace are upscaled during sleep in the presence of broad
downscaling. Furthermore, our data pointing to broad upscaling of dendritic spines in the amygdala during sleep
compared to broad downscaling in the hippocampus indicates that synapses in two key areas of the emotional
memory circuit are differentially regulated. There is a critical knowledge gap regarding the molecular pathways
involved in dendritic spine upscaling and downscaling during sleep. The proposed studies will use a
combination of state-of-the-art single nucleus RNA sequencing, spatial transcriptomics and targeted mass
spectrometry along with a novel transgenic mouse model, and complementary human brain postmortem
studies, to create a much-needed foundation of molecular signaling pathways involved in upscaling and
downscaling of synapses in the fear memory circuit during sleep and identify new molecules involved in this
process. Thus, the aims of this proposal will significantly leverage the expertise and technological capabilities
uniquely offered through the Molecular Center of Health and Disease- COBRE. The expected data will serve
as a foundation for future studies examining disruption of these pathways in psychiatric disorders, and studies
designed to identify novel targets for therapeutic strategies.

## Key facts

- **NIH application ID:** 10802290
- **Project number:** 5P20GM144041-02
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** Barbara Gisabella
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $252,749
- **Award type:** 5
- **Project period:** 2023-03-06 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802290

## Citation

> US National Institutes of Health, RePORTER application 10802290, Molecular Mechanisms of Memory Consolidation in the Amygdala-Hippocampal Circuit (5P20GM144041-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10802290. Licensed CC0.

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