# Artificially modulating memories to alleviate psychiatric disease-like states

> **NIH NIH DP5** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $412,500

## Abstract

PROJECT SUMMARY / ABSTRACT
Chronic stress affects numerous brain areas involved in memory, emotion, and motivation, such as the
hippocampus, amygdala, and prefrontal cortex; it abnormally alters a variety of cellular events, including
dendritic morphology and gene expression patterns; and, it can precipitate several maladaptive states, such as
depression- and anxiety-like behaviors. Yet, the neural circuitry sufficient to mitigate or even prevent such
phenotypes is unclear. In both mice and humans, the hippocampus has been implicated in storing and
retrieving positive memories and in modulating stress-related states. Promisingly, the recent work of the PI has
demonstrated that artificially stimulating cells in the hippocampus that previously were active during positive
memory formation are sufficient to increase reward-like behavior and motivation. To that end, in this DP5
proposal, a novel experimental bridge will be built between artificially activated positive memories and animal
models of psychiatric disorders. The recently developed virus system by the PI will be utilized in which the
promoter of the immediate early gene c-Fos drives the expression of the light-sensitive ion channel
channelrhodopsin-2 in a manner that is under the control of the antibiotic Doxycycline. In the absence of
Doxycycline, learning-induced neuronal activity selectively labels active c-Fos-expressing neurons with
channelrhodopsin-2, thus conferring activity-dependent and inducible labeling of, in addition to optical control
over, hippocampus cells and their corresponding axon terminals. The experimental goals of this project are
threefold and combine in vivo optogenetics, in vitro immunohistochemistry, and a battery of behavioral assays.
First, the hypothesis will be tested that optically modulating a defined set of positive or negative memory
bearing hippocampus cells is sufficient to ameliorate or mimic the effects of chronic stress at the cellular and
behavioral levels. Next, the goal is to test whether or not activating memory bearing hippocampus axon
terminals—which route distinct mnemonic information to the amygdala, prefrontal cortex, and nucleus
accumbens—can differentially modulate independent features of psychiatric disease-like states, such as social
impairments, anxiety-like, and anhedonic-related behavior. Finally, the goal is to test if chronically stimulating
positive memory bearing hippocampus cells prior to stress can prevent such maladaptive behaviors from
precipitating, while subsequently performing a brain-wide anatomical and histological analysis to identify key
cellular loci mediating memory's putative prophylactic capacity.

## Key facts

- **NIH application ID:** 10247723
- **Project number:** 5DP5OD023106-07
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Steve Ramirez
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2016-09-19 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247723

## Citation

> US National Institutes of Health, RePORTER application 10247723, Artificially modulating memories to alleviate psychiatric disease-like states (5DP5OD023106-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10247723. Licensed CC0.

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