Excitability of cortical neurons depends upon a powerful tonic conductance in inhibitory networks.

Abstract

Layer 4 of the mouse somatosensory (barrel) cortex has a diversity of interneuron cell types. Tonic inhibition in other regions is cell type-specific and mediated, in part, by δ-subunit containing, extrasynaptic, GABA(A) receptors. We have investigated tonic inhibition in LTS cells, a major type of inhibitory neuron, and excitatory cells in layer 4 of the mouse barrel cortex using 4,5,6,7-tetrahydroisothiazolo-[5,4-c]pyridine-3-ol (THIP), a superagonist of these receptors. Bath application of 20 µM THIP produced baseline shifts, which indicates activation of tonic inhibition of both excitatory and LTS cells. The baseline shift was significantly larger in LTS cells. This finding of greater induced current in LTS cells was paralleled by a significantly greater increase in conductance with THIP application in LTS cells. The increase in conductance resulted in LTS cells requiring more current to reach threshold. Because of the differential effects of tonic inhibition on LTS cells and excitatory cells, bath application of THIP increased the network excitability, measured by multi-unit recordings. Thus, the network effect of tonic inhibition in horizontal layer 4 circuits is a paradoxical increase in excitation.