# Closed-loop optogenetic control of gamma oscillations and emotional learning

> **NIH NIH R01** · RUTGERS THE STATE UNIV OF NJ NEWARK · 2021 · $387,500

## Abstract

Project Summary
Significance. The ability to learn that some stimuli or situations are associated with dangerous or rewarding
outcomes is generally advantageous. However, such learning can also lead to a self-reinforcing cycle of
harmful behaviors. Thus, it would be useful to achieve control over the network mechanisms that regulate the
acquisition and expression of learned emotional behaviors. This is the objective we pursue here.
Background. Principal basolateral amygdala (BLA) neurons are essential for the acquisition and expression of
conditioned emotional behaviors. Yet, remarkably few of them are activated by emotionally-valenced stimuli.
The solution to this paradox resides in the synchronizing influence of gamma. Indeed, gamma drastically
increases firing synchrony, amplifying the impact of BLA cells on their targets. Yet, it barely alters BLA firing
rates. Thus, we will study the impact of boosting or dampening BLA gamma on emotional learning. To this end,
we will combine optogenetics with programmable multi-channel signal processors, known as “field programma-
ble gate arrays” (FPGAs). Unlike computers, FPGAs allow nearly instantaneous signal analysis and conditional
light stimulus delivery, providing unprecedented control over fast neuronal events like gamma, in real time.
Approach. Parvalbumin (PV)-expressing interneurons play a critical role in the genesis of gamma. Thus,
expression of the excitatory opsin Chronos will be restricted to PV cells, by infusing the virus AAV5-hSyn-
FLEX-Chronos-GFP in the BLA of PV-cre rat. Then, to boost or dampen gamma, the optogenetic excitation of
PV cells will be timed to coincide with their preferred or non-preferred gamma firing phase, respectively.
Proposed work: In Aim #1, we will determine what gamma sub-band is most strongly expressed in the BLA
and in relation to what events (conditioned stimuli or responses). We will record unit and LFP activity while rats
learn that different conditioned stimuli predict reward delivery (CS-R) or an impending footshock (CS-S). Our
pilot data indicates that the largest changes in gamma power occur in the mid-gamma band and that mid-
gamma is differentially related to distinct conditioned responses (CRs). Based on these results, in Aim #2, we
will test whether enhancing or dampening BLA mid-gamma during the CS-R or CS-S facilitates or impairs the
expression of appetitive and defensive CRs. Last, in Aim 3, we will test whether enhancing or dampening BLA
gamma after training facilitates or impairs the consolidation of appetitive and defensive CRs. Indeed, we
previously found that in the 30 min following an emotionally arousing learning experience, mid-gamma power
increases in the BLA and that the magnitude of this increase correlates with individual variations in memory
recall. In Aims 2-3, control groups will include random groups where the same trains of light stimuli will be
delivered irrespective of ongoing gamma, no-opsin groups where the virus will only dr...

## Key facts

- **NIH application ID:** 10152676
- **Project number:** 5R01MH119854-03
- **Recipient organization:** RUTGERS THE STATE UNIV OF NJ NEWARK
- **Principal Investigator:** DENIS PARE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $387,500
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10152676

## Citation

> US National Institutes of Health, RePORTER application 10152676, Closed-loop optogenetic control of gamma oscillations and emotional learning (5R01MH119854-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10152676. Licensed CC0.

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