# Spatial transcriptomics mapping of basal ganglia to understand critical periods for sensorimotor learning

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $429,000

## Abstract

Summary
The basal ganglia comprise key brain structures for generating and refining motor sequences necessary for a
variety of complex behaviors that are acquired through procedural learning. These skills are often best learned
during early developmental critical periods. Prior work has shown that practicing these skills drives acute
changes in gene expression within the underlying basal ganglia microcircuit. This behavior-linked transcriptional
activation is observed in juveniles during the sensorimotor critical period but also occurs in adults after the critical
period has closed, suggesting that it is not specific to learning. Remarkably, a separate transcriptional profile is
only found in juveniles and correlates with the quality of the learned skill. These observations suggest that the
spatiotemporal overlap of the behavior-linked and learning-related changes in juveniles constitute a
transcriptional program that is permissive for learning. To test this idea, the individual basal ganglia cell types in
which these programs occur, currently unknown, must be resolved. Understanding these ‘transcriptional
fingerprints’ will be key to deciphering molecular signaling pathways that support sensorimotor learning. This
project leverages a well-characterized vertebrate model, the zebra finch, in which basal ganglia transcriptional
changes linked to both practice and learning have been demonstrated via bulk sequencing of the entire region,
but have not yet been traced to distinct basal ganglia cell types. Thus, one major aim is to identify and compare
single-cell gene transcripts from behaviorally activated and non-activated basal ganglia, during and after the
critical period, in order to identify specific cell types and cell signaling pathways undergoing behaviorally
regulated changes, including those that support learning. In this species, only males undergo sensorimotor
learning so comparison to the analogous regions in female brains will highlight the most relevant changes. The
second goal is to select key cell type identifiers as well as molecules implicated in the sensorimotor learning
process and develop probes to map their spatial expression in samples of the intact microcircuit using
multiplexed error-robust fluorescence in situ hybridization (MERFISH). Together, these two integrated aims will
illuminate how the basal ganglia changes over the course of repeated behavioral refinement to enable optimal
sensorimotor learning. This work has direct implications for better understanding of the mechanisms that underlie
the effectiveness of human behavioral therapies and may highlight pharmaco-therapeutic targets to improve
treatment efficacy in brain disorders ranging from autism to stroke to cerebral palsy.

## Key facts

- **NIH application ID:** 10378230
- **Project number:** 1R21NS123763-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** STEPHANIE ANN WHITE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378230

## Citation

> US National Institutes of Health, RePORTER application 10378230, Spatial transcriptomics mapping of basal ganglia to understand critical periods for sensorimotor learning (1R21NS123763-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10378230. Licensed CC0.

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