Primary somatosensory cortex bidirectionally modulates sensory gain and nociceptive behavior in a layer-specific manner

Katharina Ziegler, Ross Folkard, Antonio J. Gonzalez, Jan Burghardt, Sailaja Antharvedi-Goda, Jesus Martin-Cortecero, Emilio Isaías-Camacho, Sanjeev Kaushalya, Linette Liqi Tan, Thomas Kuner, Claudio Acuna, Rohini Kuner, Rebecca Audrey Mease () and Alexander Groh ()
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Katharina Ziegler: Heidelberg University
Ross Folkard: Heidelberg University
Antonio J. Gonzalez: Heidelberg University
Jan Burghardt: Heidelberg University
Sailaja Antharvedi-Goda: Heidelberg University
Jesus Martin-Cortecero: Heidelberg University
Emilio Isaías-Camacho: Heidelberg University
Sanjeev Kaushalya: Heidelberg University
Linette Liqi Tan: Heidelberg University
Thomas Kuner: Heidelberg University
Claudio Acuna: Heidelberg University
Rohini Kuner: Heidelberg University
Rebecca Audrey Mease: Heidelberg University
Alexander Groh: Heidelberg University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract The primary somatosensory cortex (S1) is a hub for body sensation of both innocuous and noxious signals, yet its role in somatosensation versus pain is debated. Despite known contributions of S1 to sensory gain modulation, its causal involvement in subjective sensory experiences remains elusive. Here, in mouse S1, we reveal the involvement of cortical output neurons in layers 5 (L5) and 6 (L6) in the perception of innocuous and noxious somatosensory signals. We find that L6 activation can drive aversive hypersensitivity and spontaneous nocifensive behavior. Linking behavior to neuronal mechanisms, we find that L6 enhances thalamic somatosensory responses, and in parallel, strongly suppresses L5 neurons. Directly suppressing L5 reproduced the pronociceptive phenotype induced by L6 activation, suggesting an anti-nociceptive function for L5 output. Indeed, L5 activation reduced sensory sensitivity and reversed inflammatory allodynia. Together, these findings reveal a layer-specific and bidirectional role for S1 in modulating subjective sensory experiences.

Date: 2023
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DOI: 10.1038/s41467-023-38798-7

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