# Somatosensory control of thalamic relay neurons is regulated by two distinct layer 6 feedback systems

**Authors:** Josephine Ansorge, Denise Manahan-Vaughan

PMC · DOI: 10.1016/j.isci.2025.114427 · iScience · 2025-12-12

## TL;DR

The study reveals how two different brain pathways control how touch information is processed in the thalamus, depending on the situation.

## Contribution

Discovery of two distinct layer 6 feedback systems regulating thalamic relay neurons in a context-dependent manner.

## Key findings

- Photoinactivation of S1L6B-Drd1 neurons suppressed POm activity during whisker deflection.
- S1L6-Ntsr1 neurons showed context-dependent effects on POm and VPM activity.
- A novel projection from S1L6-Drd1 neurons to zona incerta was identified.

## Abstract

The medial posterior (POm) and ventral posterior medial (VPM) thalamic nuclei sort and filter somatosensory information that is sent to the primary somatosensory cortex (S1). Corticothalamic feedback from distinct cell populations of S1 layer 6 (S1L6) targets both POm and VPM. To differentiate their roles, electrophysiological recordings were conducted in awake mice during the photoinactivation of S1L6B-Drd1-expressing neurons (that project to POm), or S1L6-Ntsr1-expressing neurons (that project to POm and VPM). Photoinactivation of either pathway suppressed POm activity when whiskers were deflected, regardless of whisking state, but S1L6-Ntsr1-POm inputs were most affected when whisker deflection occurred during non-whisking. Conversely, S1L6-Ntsr1-VPM inputs responded to whisker deflections during whisking. We identified a novel projection from S1L6-Drd1-expressing neurons to the zona incerta, indicating a role for this GABAergic structure in a corticothalamic circuit that modulates POm. These results indicate corticothalamic control of somatosensory thalamus is regulated, in a context-dependent manner, by two distinct S1L6 feedback systems supporting precision and fine-tuning of somatosensory perception.

•S1L6 Drd1 and Ntsr1-expressing cells were inhibited optogenetically during whisking in mice•Specific roles for S1L6-thalamic inputs to POm/VPM during whisker deflection were identified•Neuroanatomical tracing revealed a projection from S1L6 Drd1-neurons to zona incerta•Drd1/Ntsr1 neurons regulate somatosensory thalamus in a nucleus and context-dependent manner

S1L6 Drd1 and Ntsr1-expressing cells were inhibited optogenetically during whisking in mice

Specific roles for S1L6-thalamic inputs to POm/VPM during whisker deflection were identified

Neuroanatomical tracing revealed a projection from S1L6 Drd1-neurons to zona incerta

Drd1/Ntsr1 neurons regulate somatosensory thalamus in a nucleus and context-dependent manner

Biological sciences; Natural sciences; Neuroscience; Sensory neuroscience; Systems neuroscience

## Linked entities

- **Genes:** DRD1 (dopamine receptor D1) [NCBI Gene 1812], NTSR1 (neurotensin receptor 1) [NCBI Gene 4923]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Drd1 (dopamine receptor D1) [NCBI Gene 13488] {aka C030036C15Rik, Drd-1, Drd1a, Gpcr15}, Ntsr1 (neurotensin receptor 1) [NCBI Gene 18216] {aka NT-1R, NTR-1, NTR1}
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12796580/full.md

## References

92 references — full list in the complete paper: https://tomesphere.com/paper/PMC12796580/full.md

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Source: https://tomesphere.com/paper/PMC12796580