# Role of cholecystokinin-expressing interneurons in the oscillatory control of experience-dependent fear behavior

> **NIH NIH R21** · TUFTS UNIVERSITY BOSTON · 2022 · $247,500

## Abstract

PROJECT SUMMARY
An important functional role for oscillatory brain activity is supported by the observation that brain oscillations
at specific frequencies correlate with specific behavioral and mental states, including states of fear. The precise
mechanistic basis for these correlations is unclear. Achieving a deeper mechanistic understanding requires the
identification of specific types of neurons that mediate causal relationships between specific patterns of
oscillatory activity and specific behavioral and mental states. Different patterns of oscillatory activity have been
detected in the basolateral amygdala (BLA) during the expression versus the suppression of experience-
dependent fear behavior. Oscillatory activity that causes the suppression of experience-dependent fear
behavior is controlled by parvalbumin-expressing (PV+) interneurons located in the BLA. PV+ interneurons
exert strong control over both oscillatory activity and functional output of BLA circuits through inhibitory
synapses that they make onto the soma of BLA projection neurons. Perisomatic inhibitory synapses in the BLA
are also made by interneurons that express cholecystokinin (CCK+ interneurons). Based on previous findings,
CCK+ interneurons in the BLA could play a role that is opposite from the role played by PV+ interneurons in
the BLA with regards to the oscillatory control of experience-dependent fear behavior. The goal of this study is
to determine if CCK+ interneurons in BLA control oscillatory activity that causes increased behavioral
expression of experience-dependent fear. To achieve this goal, mice will be subjected to contextual fear
conditioning, contextual fear extinction, and contextual fear retrieval. CCK+ interneurons in the BLA of these
mice will be silenced with an optogenetic approach. Silencing CCK+ interneurons is hypothesized to decrease
the behavioral expression of the fear memory, as measured by observing freezing behavior, and to also decrease
oscillatory activity that causes experience-dependent fear behavior, as measured by recording local-field
potentials in the BLA. In addition, the spiking activity of single-units in the BLA will be recorded and analyzed
in order to identify neuronal mechanisms that might underlie the relationship between oscillatory and
behavioral changes. Completion of this study will increase the mechanistic understanding of how brain
oscillations control experience-dependent fear behavior, and might lead to improved treatment options for
patients suffering from excessive fear, for example as a result of post-traumatic stress disorder.

## Key facts

- **NIH application ID:** 10348491
- **Project number:** 1R21MH128802-01
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Leon Reijmers
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $247,500
- **Award type:** 1
- **Project period:** 2022-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348491

## Citation

> US National Institutes of Health, RePORTER application 10348491, Role of cholecystokinin-expressing interneurons in the oscillatory control of experience-dependent fear behavior (1R21MH128802-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10348491. Licensed CC0.

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