# Role of thalamic modulation in motor learning

> **NIH NIH K99** · STANFORD UNIVERSITY · 2023 · $122,931

## Abstract

PROJECT SUMMARY
 Learning and executing motor skills are crucial functions of the brain and involve the coordinated activity of
multiple brain regions. Traditionally, the motor cortex (MCtx), the basal ganglia (BG), and the cerebellum (CB)
have been considered key motor control regions of the brain, and plasticity within these regions are known to
support motor learning. In addition, neuromodulation, such as from adrenergic neurons in the locus coeruleus
(LC), is critical for proper behavior and learning. Despite the key role these regions play in controlling
movements and their implication in movement disorders, we are only beginning to understand how motor
signals from these regions interact with each other. Anatomically, the thalamus serves as a common target
structure for MCtx, BG, and CB, yet conventionally, the thalamus has been viewed as a passive relay station.
However, there is emerging evidence that the thalamus can functionally integrate and modulate these diverse
motor signals. How thalamic neurons respond to motor inputs, the role of motor thalamus in motor learning,
and how adrenergic signaling modulates thalamic activity are largely undefined. My central hypothesis is that
the motor thalamus serves as a point of convergence for motor signals from MCtx, BG, and CB, as well as
neuromodulatory input from LC, allowing it to functionally integrate these inputs to control movements and
promote motor learning. I propose to use a combination of in vivo deep-brain imaging and novel fluorescent
sensors for intracellular signaling in mice performing motor tasks, as well as slice electrophysiology, to
measure the activity of motor thalamus during movement and determine how such activity is modulated by
adrenergic input from LC. These approaches will allow me to define the inputs to motor thalamus and measure
thalamic activity during movement and motor learning (Aim 1), determine the functional role of motor thalamus
and its inputs in motor control (Aim 2), and determine how adrenergic signaling modulates thalamic activity
during motor learning (Aim 3). Results from this study will not only clarify the role of the motor thalamus in
motor control and motor learning but also provide an understanding of how adrenergic neuromodulation
influences thalamic activity during behavior. This is of critical importance, as abnormal thalamic activity and
disrupted adrenergic signaling are characteristic features of motor diseases. The experiments proposed in this
study will span the mentored K99 and independent R00 phase of this award, with the K99 phase being focused
on defining the activity and role of motor thalamus during motor learning and the R00 phase focused on
understanding how adrenergic input to the thalamus modulates motor signals. My proposed training plan builds
on my experience in two-photon in vivo imaging and mouse behaviors and will add training in slice
electrophysiology. In addition, my expert mentoring team will also provide guidance in ...

## Key facts

- **NIH application ID:** 10740323
- **Project number:** 1K99NS130078-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Richard Roth
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $122,931
- **Award type:** 1
- **Project period:** 2023-08-20 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10740323

## Citation

> US National Institutes of Health, RePORTER application 10740323, Role of thalamic modulation in motor learning (1K99NS130078-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10740323. Licensed CC0.

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