Tonic excitation or inhibition is set by GABAA conductance in hippocampal interneurons

Abstract

Inhibition is a physiological process that decreases the probability of a neuron generating an action potential. The two main mechanisms that have been proposed for inhibition are hyperpolarization and shunting. Shunting results from increased membrane conductance, and it reduces the neuron-firing probability. Here we show that ambient GABA, the main inhibitory neurotransmitter in the brain, can excite adult hippocampal interneurons. In these cells, the GABA_A current reversal potential is depolarizing, making baseline tonic GABA_A conductance excitatory. Increasing the tonic conductance enhances shunting-mediated inhibition, which eventually overpowers the excitation. Such a biphasic change in interneuron firing leads to corresponding changes in the GABA_A-mediated synaptic signalling. The described phenomenon suggests that the excitatory or inhibitory actions of the current are set not only by the reversal potential, but also by the conductance.