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Circuit-selective cell-autonomous regulation of inhibition in pyramidal neurons by Ste20-like kinase.

Cell reports

Authors: Pedro Royero, Anne Quatraccioni, Rieke Früngel, Mariella Hurtado Silva, Arco Bast, Thomas Ulas, Marc Beyer, Thoralf Opitz, Joachim L Schultze, Mark E Graham, Marcel Oberlaender, Albert Becker, Susanne Schoch, Heinz Beck

Maintaining an appropriate balance between excitation and inhibition is critical for neuronal information processing. Cortical neurons can cell-autonomously adjust the inhibition they receive to individual levels of excitatory input, but the underlying mechanisms are unclear. We describe that Ste20-like kinase (SLK) mediates cell-autonomous regulation of excitation-inhibition balance in the thalamocortical feedforward circuit, but not in the feedback circuit. This effect is due to regulation of inhibition originating from parvalbumin-expressing interneurons, while inhibition via somatostatin-expressing interneurons is unaffected. Computational modeling shows that this mechanism promotes stable excitatory-inhibitory ratios across pyramidal cells and ensures robust and sparse coding. Patch-clamp RNA sequencing yields genes differentially regulated by SLK knockdown, as well as genes associated with excitation-inhibition balance participating in transsynaptic communication and cytoskeletal dynamics. These data identify a mechanism for cell-autonomous regulation of a specific inhibitory circuit that is critical to ensure that a majority of cortical pyramidal cells participate in information coding.

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

PMID: 36476865

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