# The role of genetic and activity dependent cues in the generation of 5HT3aR interneuron diversity

> **NIH NIH P01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $361,211

## Abstract

Project Summary (Project 1)
!
Project One will explore the complementary influences of intrinsic genetic programs and activity to the
development of 5HT3aR interneurons. Aim 1 will examine the transcriptional and epigenetic function of Prox1
in 5HT3aR cINs. By examining the targets of Prox1 in 5HT3aR cells we will provide insight in the genetic
mechanisms that generate these populations, as well as the basis by which Prox1 directs
synaptogenesis,morphology and circuit connectivity (Aim 2). Will examine how activity alters gene expression
with 5HT3aR cINs and the role of L-type Ca2+ channels in the activity-dependent development and plasticity of
5HT3aR cINs. This aim will proceed in two subparts: (subaim 2a) Where we will use intersectional genetic
methods to target the five L1-3 5HT3aR interneuronal subtypes, by cell autonomously suppressing (Kir2.1) or
increasing (NachBac) their activity and use RNA-seq to determine how it alters gene expression within specific
subpopulations. And (subaim 2b) Where we will use conditional genetic methods to remove L-Type Ca2+
function (Cav1.2, Cav1.3) from 5HT3aR cINs. This aim will yield insights into the cell autonomous requirement
for L-type channels in 5HT3aR cIN populations. , (Aim 3). Will examine the establishment the developmental
connectivity of 5HT3aR cINs. This aim will also proceed with two subparts: (subaim 3a) which will examine the
development of interneuron/pyramidal cells ensembles within the superficial cortex. This will use a combination
of mono-synaptic rabies tracing, genetic encoded Calcium-sensors (gCaMP/rCaMP) and optogenetics to
examine the afferent and efferent connectivity of specific 5HT3aR cIN subtypes in L1. Of particular interest will
be to compare how this circuitry compares with that seen in the mature auditory and somatosensory cortices
and (subaim 2b) which extend our examination of Prox1 and L-Type Ca2+ channels affect the formation of the
connectivity of the 5HT3aR cINs during development . Specifically, examination as to how changes in the
intrinsic genetic program (Aim1) or activity-mediated maturation (Aim 2) manifest in changes in the circuit
function of 5Ht3aR interneurons (as explored by Dr. Rudy in Project 2) and the ability of cholinergic afferents
and L1 interneurons to influence plasticity and attention in a Go-No go task where mice are examined for their
responses to salient versus non-salient cues (Froemke in Project 3). Together project 1 will provide insight into
how assembly of L1-3 circuits that are critically dependent upon 5Ht3aR interneurons impact adult connectivity,
plasticity and function.!

## Key facts

- **NIH application ID:** 10098071
- **Project number:** 5P01NS074972-08
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** GORDON J FISHELL
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $361,211
- **Award type:** 5
- **Project period:** 2012-09-30 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10098071

## Citation

> US National Institutes of Health, RePORTER application 10098071, The role of genetic and activity dependent cues in the generation of 5HT3aR interneuron diversity (5P01NS074972-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10098071. Licensed CC0.

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