# Linking interneuron-mediated circuit regulation with sleep-dependent plasticity and memory storage in the hippocampus

> **NIH NIH RF1** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $1,366,868

## Abstract

Project summary: Synaptic plasticity in brain structures like the hippocampus has been hypothesized to
underlie an essential brain function - consolidating transient experiences into long-lasting memories. The
importance of sleep for promoting long-term memory storage, and the disruptive effect of sleep deprivation on
memory, have been appreciated for nearly a century. However, it remains unclear how sleep-associated
changes in the activity of specific brain circuits contribute to synaptic plasticity in the hippocampus and other
structures. The studies proposed here will test a novel hypothesis – that sleep and sleep loss differentially affect
memory consolidation through their differential effects on separate subpopulations of hippocampal interneurons.
We will use a simple behavioral paradigm for studying sleep-dependent memory consolidation in mice
(contextual fear memory; CFM) in combination with state-targeted pharmacogenetic and optogenetic
manipulations of parvalbumin-expressing (PV+) and somatostatin-expressing (SOM+) hippocampal
interneurons. In the context of these experimental manipulations, we will measure downstream effects on sleep-
associated CFM consolidation, hippocampal network activity, microcircuit-level changes in neuronal structure,
and biochemical changes in genetically-defined cell populations. We will first assess the effects of learning itself
(contextual fear conditioning; CFC) and subsequent sleep or sleep deprivation (SD) on neuronal morphology
using cell type-specific Brainbow labeling, and intracellular processes using cell type-specific translating
ribosome affinity purification (TRAP). We will then determine how state-specific manipulations of hippocampal
PV+ interneuron activity (which disrupt of rescue sleep-dependent CFM consolidation) affect these sleep-
dependent processes. Finally, we will test the hypothesis that SD disrupts CFM consolidation by selectively
activating SOM+ interneurons in the hippocampus, leading to suppression of activity in neighboring neurons. We
will test whether pharmacogenetic activation of these neurons (mimicking effects of SD) disrupts CFM
consolidation in freely-sleeping mice, and whether inhibition of these neurons during SD (mimicking effects of
sleep) rescues CFM consolidation. We will then assess the effects of changing SOM+ interneuron activity levels
on post-CFC changes in hippocampal network activity patterns, neuronal morphology, and cell biology. Together,
these studies will test the necessity and sufficiency of state-dependent activity in defined hippocampal neuron
populations for long-term storage of new memories.

## Key facts

- **NIH application ID:** 10053374
- **Project number:** 1RF1NS118440-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** SARA J ATON
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,366,868
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053374

## Citation

> US National Institutes of Health, RePORTER application 10053374, Linking interneuron-mediated circuit regulation with sleep-dependent plasticity and memory storage in the hippocampus (1RF1NS118440-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10053374. Licensed CC0.

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