Tonic GABAA conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network

Abstract

The spiking output of interneurons is key for rhythm generation in the brain. However, what controls interneuronal firing remains incompletely understood. Here we combine dynamic clamp experiments with neural network simulations to understand how tonic GABAA conductance regulates the firing pattern of CA3 interneurons. In baseline conditions, tonic GABAA depolarizes these cells, thus exerting an excitatory action while also reducing the excitatory postsynaptic potential (EPSP) amplitude through shunting. As a result, the emergence of weak tonic GABAA conductance transforms the interneuron firing pattern driven by individual EPSPs into a more regular spiking mode determined by the cell intrinsic properties. The increased regularity of spiking parallels stronger synchronization of the local network. With further increases in tonic GABAA conductance the shunting inhibition starts to dominate over excitatory actions and thus moderates interneuronal firing. The remaining spikes tend to follow the timing of suprathreshold EPSPs and thus become less regular again. The latter parallels a weakening in network synchronization. Thus, our observations suggest that tonic GABAA conductance can bidirectionally control brain rhythms through changes in the excitability of interneurons and in the temporal structure of their firing patterns.