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 pro-cessing. 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) me-diates 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-ex-pressing interneurons, while inhibition via somatostatin-expressing interneurons is unaffected. Computa-tional 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 regu-lated 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 -autono-mous regulation of a specific inhibitory circuit that is critical to ensure that a majority of cortical pyramidal cells participate in information coding.

Automated summary

Maintaining a balance between excitation and inhibition is crucial for neuronal information processing. A study has shown that Ste20-like kinase (SLK) mediates the cell-autonomous regulation of this balance in the thalamocortical feedforward circuit, promoting stable excitatory-inhibitory ratios and ensuring robust and sparse coding in cortical pyramidal cells.