# Circuit Assembly in the developing thalamus

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2020 · $465,903

## Abstract

Project Summary/Abstract
The thalamic reticular nucleus (TRN), is a shell like structure that surrounds the dorsal thalamus and serves as
a key inhibitory interface for the bidirectional signaling between thalamus and the neocortex. Together with
inputs from thalamus, cortex, and cholinergic nuclei of brainstem and basal forebrain, the TRN regulates many
aspects of sensory, motor, and cognitive processing. When the connections between these structures are
disrupted by disease, degeneration, or trauma, they have devastating consequences. In fact, many adult and
childhood neurological disorders have at their core, a disturbance in TRN signaling and circuitry. Despite its
key role in thalamocortical function, remarkably little is known about how reticular circuitry emerges during
development and becomes operational. To address this substantive gap in knowledge we developed a robust
mouse model as an experimental platform to visualize, manipulate, and dissect emergent and developing
reticular circuitry. We plan to conduct anatomical, electrophysiological, and optogenetic experiments in
genetically modified mice that allow for the visualization and experimental manipulation of specific cell types
arising from the TRN, first-order thalamic sensory nuclei, layer VI of cortex, and cholinergic nuclei of brainstem
and basal forebrain. The goals of this proposal focus on three unanswered questions about TRN development.
First, how are the sensory sectors of TRN established; do inputs from primary sensory thalamic nuclei and
corresponding regions of cortex innervate TRN diffusely and then segregate to form modality specific
domains? Second, what is the sequence and pattern of driver and modulator innervation of TRN; do driver-like
inputs from sensory thalamic nuclei such as the dorsal lateral geniculate nucleus, arrive prior to modulatory
input from cortex, or brainstem and basal forebrain? Third, how and when do feed-forward and feedback
circuits linking TRN to thalamus and cortex emerge during development to control thalamocortical signaling?
Finally, for each of these questions, we plan to take a loss of function approach to assess whether the absence
of sensory input (vision) affects the development, form, and function of reticular circuitry. These studies will
provide valuable information about the organizing principles that guide the emergence of reticular circuitry in
the neonatal brain, and perhaps reveal a new understanding into childhood disorders that result from abnormal
patterns of connectivity.

## Key facts

- **NIH application ID:** 9905521
- **Project number:** 5R01EY012716-21
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** WILLIAM GUIDO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $465,903
- **Award type:** 5
- **Project period:** 2001-05-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9905521

## Citation

> US National Institutes of Health, RePORTER application 9905521, Circuit Assembly in the developing thalamus (5R01EY012716-21). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9905521. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*