# Mechanisms of Transplanted Cortical Interneuron Survival and Function

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $117,723

## Abstract

Project Summary
Cortical interneurons (cINs) are inhibitory cells that are born in surplus far from the cortex. During prenatal
timepoints, cIN precursors migrate into the mouse visual cortex (V1) where only a fraction are selected to
survive. Once integrated into the V1 circuit, cINs expressing parvalbumin (PV) or somatostatin (SST) trigger a
temporally restricted period of plasticity that is required for normal visual experience. The underlying molecular
factors and the role cellular activity plays in the selection of cIN survival and cIN-mediated plasticity are not
fully understood. PV and/or SST cIN precursors that are heterochronically transplanted into a recipient cortex
have been shown to follow a similar timeline for survival and create a temporally restricted window of plasticity
in the “host” that follows the timeline of the “donor”, revealing that transplanted cINs develop at a normal rate
and may be used as a proxy for cIN development. Here, I propose to use cIN transplantation to study the
transcriptional changes and the molecular factors responsible in selecting cINs for survival (Aim 2) and for the
capacity of cINs to induce plasticity (Aim 1). During the mentored phase of this award, Aim 1a will study the
differential expression of transcripts from transplanted PV and SST cINs as they trigger plasticity in the host
visual cortex. Aim 1b will compare these transcriptional changes to the transplant recipient’s PV and SST cINs
to test whether similar genes are expressed and to characterize how host cINs are being affected at the
molecular level by transplant-mediated plasticity. Aim 1c will compare the transcriptional changes in
transplanted PV and SST cINs to endogenous PV and SST cINs at corresponding developmental ages over
the juvenile critical period, to compare the temporal gene expression between transplanted CINs as they open
a second critical period and endogenous cINs as they open the juvenile critical period. During the independent
phase of this award, Aim 2a will track the excitability of transplanted cINs in vivo during the period of
programmed cell death to identify a timeline of activity related to the selection for survival. Aim 2b will generate
gene expression profiles over this timeline to characterize transcriptional signatures for survival versus death.
To determine whether the genes of interest from Aim 2b are required for the selection of survival, their
expression will be manipulated in Aim 2c. Transplanted cINs will be targeted with RNAi and their activity and
survival will be measured. This proposal will identify novel therapeutic targets necessary for the formation of
functional visual circuits and for developing more accessible ways to promote cortical plasticity.

## Key facts

- **NIH application ID:** 10425147
- **Project number:** 1K99EY033976-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Benjamin Rakela
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $117,723
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10425147

## Citation

> US National Institutes of Health, RePORTER application 10425147, Mechanisms of Transplanted Cortical Interneuron Survival and Function (1K99EY033976-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10425147. Licensed CC0.

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