Generation of physiological and pathological high frequency oscillations: the role of perisomatic inhibition in sharp-wave ripple and interictal spike generation

•Tonic excitation of reciprocally connected PVBCs evokes ripple frequency firing.•Physiological ripples are primarily perisomatically generated inhibitory currents.•IISs are degenerate forms of SWRs, when inhibition collapses.•Altered excitability and E/I balance accelerate buildup during initiation of an IIS.•Fast ripples are population spikes of pseudo-synchronized PCs bursts.

Sharp-wave-ripple complexes (SWRs) and interictal-spikes are physiological and pathological forms of irregularly occurring transient high activity events in the hippocampal EEG. They share similar features and carry high-frequency oscillations with different spectral features. Recent results reveal similarities and differences in the generation of the two types of transients, and argue that parvalbumin containing basket cells (PVBCs) are crucial in synchronizing neuronal activity in both cases. SWRs are generated in the reciprocally connected network of inhibitory PVBCs, while in the pathological case, synchronous failure of perisomatic inhibition triggers massive pyramidal cell burst firing. While physiological ripple oscillation is primarily the result of phasic perisomatic inhibitory currents, pathological high-frequency ripples are population spikes of partially synchronous, massively bursting, uninhibited pyramidal cells.

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