GABAB Inhibition through Feedback Is Involved in the Synchronization of Interictal Spikes in the Cortex

Recent studies have significantly expanded our understanding of the functions of GABAergic interneurons in cortical neural networks. Interneurons of specific classes are involved in generating interictal activity in the cortex not only in certain types of pathology, but also in conditions in which inhibition is mediated mainly via GABA B receptors. Interictal activity consists of high-amplitude spikes, where a short excitatory phase is followed by a long inhibitory phase occurring almost simultaneously in different parts of the cortex. Highamplitude spikes reflect the synchronous action of excitatory neurons in a local area, while synchronous activity in remote areas is determined by feedback between pyramidal cells and interneurons, when the activity of a large mass of neurons occurs simultaneously within a narrow time interval. Synchronization of interictal spikes involves Martinotti cells, as well as parvalbumin, neurogliaform, and vasoactive intestinal peptide-expressing interneurons, which, as experimental data show, also inhibit via GABA B receptors. Several mechanisms are now known which synchronize neuron activity in cortical neural networks: via electrical connections, volume conduction, and synaptic feedback – both between pyramidal neurons and interneurons and between interneurons. We propose that the mechanism of synchronization of interictal spikes in cortical neural networks operates as follows. This mechanism appears to operate in the same way both in local neural networks and over distances. When excitation occurs, it is followed by inhibition mediated by feedback; this limits the excitation period and thus creates a time window for integration, and this also occurs in neighboring cortical neural networks. At the initial stage, the amplitudes of interictal spikes are small and nonsimultaneous in different parts of the cortex. As time progresses, ever more pyramidal neurons become active during the time window, thus increasing the amplitude of the interictal spike, in turn increasing inhibition. Increased inhibition due to feedback ultimately begins to affect neighboring neural networks, with the result that interictal spikes appear almost simultaneously in different parts of the cortex. This produces a significant lengthening of postspike inhibition, as inhibition within a neural network is supplemented by inhibition from neighbors via inhibitory feedback.