# Identification of neuronal ensembles mediating fear generalization in the infralimbic cortex

> **NIH NIH R15** · VASSAR COLLEGE · 2021 · $438,107

## Abstract

PROJECT SUMMARY
Posttraumatic stress disorder (PTSD) afflicts 8% of the US population. One prominent symptom of PTSD is the
over-generalization of traumatic memories. Generalization refers to the transfer of learned responding to
stimuli that are similar, but not identical, to the original conditioned stimulus (CS). Despite the importance of
understanding generalization, in both basic memory processing and PTSD, very little is known about the
neuronal substrates. Memory is thought to be encoded in sparse, distributed groups of neurons known as
“neuronal ensembles.” Over time, neuronal ensembles supporting memory expression are dynamic.
Generalization is also dynamic, with a tendency to increase over time, suggesting a relationship between the
two. A major question in neuroscience is how ensemble dynamics mediate changes in the expression of
generalization over time. One brain region shown to contribute to generalization is the infralimbic cortex (IL).
Despite a known role for the IL in generalization, the identification of IL neuronal ensembles mediating
generalization processes over time is unknown. One obstacle in the way of studying neuronal ensembles is the
inherent technical difficulty in ensemble identification and manipulation. New molecular tools, such as
ArcCreERT2 x EYFP transgenic mice, for permanently “tagging” active cells (Arc/arg3.1 expression) during
learning for comparison with cells active during memory recall, has advanced the field. In Aim 1, we use
ArcCreERT2 x EYFP mice to tag cells in the IL during learning for comparison with cells activated during recall
of either the CS or after a novel tone (generalization or discrimination) at recent or remote retention intervals.
While “tagging” technology provides a window into neuronal ensemble dynamics, the resolution of the
approach is limited. To provide greater temporal resolution (subsecond) for identifying neuronal ensembles
dynamics, we incorporate in vivo Ca2+ imaging to visualize, measure, and compare coordinated IL ensemble
activity associated with fear generalization over time. In Aim 2, a causal link between global IL activity and fear
generalization will be established using chemogenetics to bi-directional modulate IL pyramidal neuron
excitation. Activity-dependent (ArcCreERT2) chemogenetics will be used to test whether the synthetic
reactivation of a small number of neurons whose activity was previously associated with generalization (i.e., a
”generalization ensemble”) is sufficient to drive generalization expression. I have outlined a research plan well-
suited for undergraduate neuroscience research. Nearly all proposed techniques have already been
successfully carried out in my lab. It is anticipated the data generated by these experiments will not only
strengthen undergraduate research at Vassar but will lead to a greater understanding of fear generalization
processes at the level of neuronal ensembles, with the hope of informing treatment strategies for PTSD.

## Key facts

- **NIH application ID:** 10292108
- **Project number:** 1R15MH127534-01
- **Recipient organization:** VASSAR COLLEGE
- **Principal Investigator:** Hadley Creighton Bergstrom
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $438,107
- **Award type:** 1
- **Project period:** 2021-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10292108

## Citation

> US National Institutes of Health, RePORTER application 10292108, Identification of neuronal ensembles mediating fear generalization in the infralimbic cortex (1R15MH127534-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10292108. Licensed CC0.

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