# Circuits underlying overgeneralization

> **NIH NIH R01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2024 · $399,750

## Abstract

Overgeneralization is a cognitive impairment commonly associated with post-traumatic stress
disorder as well as mood and anxiety disorders. Over the past 10 years of this grant, we have
accumulated several lines of evidence indicating that the dentate gyrus (DG) contributes to a
range of negative valence related behaviors including fear overgeneralization, as well as to some
of the behavioral effects of antidepressant medications. Specifically, we and others have shown
that the dentate gyrus is critical for contextual fear discrimination learning, a form a
learning that has been proposed to be mediated by pattern separation, a computational
process by which similar experiences are transformed into discrete non-overlapping neural
representations. In the current proposal we aim at bringing together these behavioral and
physiological lines of research by showing that the DG is critical for pattern separation and that
deficits in pattern separation underlie the contextual discrimination deficits often observed in mood
and anxiety disorders. Based on our preliminary results we hypothesize that strategies aimed
at improving pattern separation in the DG will be beneficial for the treatment of mood and
anxiety disorders.
Unlike most other brain regions, the adult DG contains not only mature developmentally-born
neurons but also adult-born neurons generated via a process termed adult neurogenesis. We
and others have shown that both mature granule cells (mGCs) and young adult-born granule cells
(abGCs) are critical for contextual fear discrimination learning (CFD). In the proposed studies we
will image the activity of both abGCs as well as mGCs in the DG during a contextual fear
discrimination task by using calcium imaging and miniature microscopes (miniscopes).
This imaging will be done in baseline conditions (Aim 1), after optogenetic manipulation of abGCs
to modulate DG activity (Aim 2), and after early life stress and adult manipulations of DG activity
(Aim 3).

## Key facts

- **NIH application ID:** 10769852
- **Project number:** 5R01MH068542-22
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Rene Hen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,750
- **Award type:** 5
- **Project period:** 2003-05-07 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769852

## Citation

> US National Institutes of Health, RePORTER application 10769852, Circuits underlying overgeneralization (5R01MH068542-22). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10769852. Licensed CC0.

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