# The role of Neuroligin 2 in the regulation of GABAergic interneuron activity and cortical inhibition

> **NIH NIH F30** · BAYLOR COLLEGE OF MEDICINE · 2021 · $2,500

## Abstract

Project Summary/Abstract
GABAergic interneurons are critical for the maintenance of proper levels of cortical excitability. However, very
little is known about the mechanisms involved in the control of their activity. Specifically, there is a critical need
to understand the formation and maintenance of inhibitory synaptic inputs onto interneurons. Our long-term
goal is to gain a better understanding of the molecular mechanisms involved in the control of inhibitory
interneuron activity to allow for manipulation of synaptic inhibition in neuropsychiatric disorders where cortical
activity is disrupted. The overall goal is to determine the role of Neuroligin 2 (Nlgn2) in the regulation of this
inhibition and to better understand how loss of Nlgn2 alters the activity of the inhibitory interneurons and leads
to disease. The central hypothesis is that Nlgn2 plays an essential role in the regulation of inhibition onto
GABAergic interneurons and loss of Nlgn2 in interneurons leads to functional consequences on cortical activity
that may result in neuropsychiatric symptoms. Loss of Nlgn2 in somatostatin positive (Sst+) interneurons
results in a decrease in the frequency and amplitude of synaptic inhibitory inputs onto those cells. Aim one will
combine classical synaptic physiology and pharmacology with input-specific optogenetics to identify the
synaptic mechanisms that lead to alterations in inhibitory inputs onto Sst+ interneurons. Aim two will use in
vivo Ca2+ imaging and electroencephalography (EEG) recordings to determine the functional consequences of
loss of Nlgn2 in Sst+ interneurons on both cellular activity and overall cortical activity, respectively. These
important questions have yet to be addressed due to critical barriers including the inability to specifically
manipulate inhibitory synapses onto interneurons and the inability to directly test and manipulate the
connections between subtypes of interneurons in slice electrophysiology. This proposal overcomes these
barriers due to a novel approach that utilizes viral genetics, Cre recombinase, and FlpO recombinase, and the
specific manipulation of Nlgn2, a post-synaptic protein found exclusively at inhibitory synapses. The proposed
research is expected to elucidate the molecular mechanisms involved specifically in the regulation of cortical
interneuron activity. This contribution will be significant because it will allow for the manipulation of interneuron
activity to alter levels of cortical inhibition, serving as a novel therapeutic target therapy for neuropsychiatric
diseases in the future.

## Key facts

- **NIH application ID:** 10399690
- **Project number:** 3F30MH118804-03S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Colleen Michelle Brady
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2019-03-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399690

## Citation

> US National Institutes of Health, RePORTER application 10399690, The role of Neuroligin 2 in the regulation of GABAergic interneuron activity and cortical inhibition (3F30MH118804-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10399690. Licensed CC0.

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