# Function of 5HT3aR Cortical Interneurons for Auditory Perception and Learning

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2022 · $322,962

## Abstract

Project Summary
Cortical inhibitory cells are critical for regulating information processing and synaptic plasticity in neural circuits.
This plasticity is essential for learning and memory, and is an important feature of the auditory cortex, especially
for learning the significance of sensory signals such as speech. Long-term synaptic plasticity requires sensory
experience and activation of neuromodulatory systems such as the cholinergic nucleus basalis, which conveys
behavioral context to local cortical circuits. However, little is known about how cortical interneurons are involved
in these mechanisms, or if different inhibitory cell types have different roles for developmental or adult plasticity.
Recently we developed an approach to measure long-term excitatory and inhibitory synaptic modifications in
vivo over hours to weeks. These experiments revealed that prior to experience with sounds, cortical inhibition
was initially mismatched with excitation, but becomes `balanced' with excitation after experience or training.
 [These experiments now allow us to construct a new framework for understanding the roles of 5HT3aR
and non-5HT3aR cortical interneurons during auditory behavior in mice, with a series of behavioral, imaging,
and recording experiments integrated with the larger collaborative PPG structure. We hypothesize that there are
important functional differences in these cell types, in terms of their relative contributions to auditory behavior
(Aim 1), cholinergic modulation (Aim 2), and cortical microcircuit organization and plasticity (Aim 3). Specifically,
in Aim 1 we will first examine the behavioral relevance of specific cortical interneuron subtypes, as initially-naive
mice are trained to perform an auditory detection and recognition task we have used in the lab for years. We ask
how sensory experience and behavioral training might recruit these cell types and naturally shape excitatory and
inhibitory circuit elements, using whole-cell recordings combined with 2-photon Ca2+ imaging to directly measure
excitation and various cell-type-specific sources of inhibition in vivo. In Aim 2 we examine if these cell types are
differentially affected by cholinergic modulation, perhaps due to differential sensitivity to acetylcholine or specific
wiring of cholinergic input into cortex. Finally, in Aim 3 we will make recordings in cortical brain slices, to
document how different cortical interneuron types are synaptically connected and modified for circuit operation.]
 In summary, here we will use in vivo and in vitro electrophysiology, imaging, and optogenetics to ask how
different cortical interneurons (5HT3aR vs non-5HT3aR) govern sensory processing and plasticity. The two core
concepts of these studies involve long-term synaptic plasticity, believed to be a major neural correlate of learning
and memory, and excitatory-inhibitory balance- the precise regulation of excitation by inhibitory circuits. These
processes are believed to be disrupted...

## Key facts

- **NIH application ID:** 10322666
- **Project number:** 5P01NS074972-09
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Robert Crooks Froemke
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $322,962
- **Award type:** 5
- **Project period:** 2012-09-30 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322666

## Citation

> US National Institutes of Health, RePORTER application 10322666, Function of 5HT3aR Cortical Interneurons for Auditory Perception and Learning (5P01NS074972-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10322666. Licensed CC0.

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