# Functional dissection of thalamocortical interactions through genetically-defined TRN subnetworks

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $708,383

## Abstract

PROJECT SUMMARY
 The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, plays essential roles in
sensory processing, arousal and cognition. Receiving inputs from cortical and subcortical regions, this
structure is strategically positioned to influence thalamo-cortical interactions. During quiescence, the TRN
participate in sleep rhythm generation, sleep stability and memory consolidation, while in active states, TRN
neurons contribute to sensory filtering underlying attention. Perturbed TRN function may underlie behavioral
deficits in disorders ranging from schizophrenia and autism to ADHD. Despite its importance, however, several
key challenges have limited our ability to determine exactly how TRN circuitry contributes to various brain
functions, a prerequisite for determining how it malfunctions in diseases and how its circuitry can be leveraged
for diagnostic and therapeutic purposes. This proposal aims to address this critical gap in knowledge by
capitalizing on a novel set of findings and tools that we generated. The TRN is a thin shell of GABAergic
neurons surrounding thalamic projection nuclei. Within the TRN, neurons that have distinct structural and
functional properties can be partially intermingled. This anatomical feature has been a major impediment for
functional studies, since selective targeting of TRN neurons that share structural and functional properties with
traditional methods is challenging. Using single cell RNAseq, we have recently discovered that TRN neurons
can be dissociated into two major subtypes with distinct transcriptomic profiles, anatomical localizations,
electrophysiological properties and thalamic connectivity. One group, located in the “core” region of the TRN
and can be marked by the expression of the Spp1 gene, targets first-order sensory thalamic nuclei, and the
other, located in the “shell” region of the TRN and marked by the expression of Ecel1 gene, targets higher-
order ones. We have generated transgenic mice expressing Cre recombinase in each of these two populations
individually. Here, we propose to use these new knowledge and genetic tools to answer fundamental questions
about TRN structure-function organization as well as the contribution of this brain region to sensory
processing, arousal and cognition.

## Key facts

- **NIH application ID:** 9993593
- **Project number:** 5R01NS113245-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Guoping Feng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $708,383
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993593

## Citation

> US National Institutes of Health, RePORTER application 9993593, Functional dissection of thalamocortical interactions through genetically-defined TRN subnetworks (5R01NS113245-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9993593. Licensed CC0.

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