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

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. [Display omitted] • SLK regulates excitation-inhibition balance cell-autonomously • SLK in cortical neurons regulates feedforward but not feedback inhibition • SLK selectively regulates inhibition by parvalbumin-expressing interneurons Royero et al. identify a mechanism relying on Ste20-like kinase that allows single cortical neurons to cell-autonomously adjust feedforward inhibition they receive to the cell-specific levels of excitatory input. They propose that this mechanism is critical to ensure that a majority of cortical pyramidal cells participate in information coding. [ABSTRACT FROM AUTHOR]