INTER-SITE SYNCHRONY OF RIPPLE OSCILLATIONS AS A CENTRAL GABAERGIC FUNCTION

Hippocampal oscillations in the ripple frequency (150 - 250 Hertz) are considered a biomarker for memory function, founded in a delicate balance of neuronal excitation and inhibition. However, little attention has been given to the discrete spatiotemporal profiles of ripple oscillations as they occur. Here, we first re-analyze previously published in vivo recordings of mouse hippocampal ripples and discover that ripple oscillations cross-correlate across the hippocampus to a consistently variable degree. This "inter-site synchrony" is surprisingly saturated in a mouse model of Alzheimer's disease. We then reproduce synchronous ripple oscillations in multi-electrode array recordings of ex vivo brain slices and dissect the synaptic mechanisms supporting synchronization at distant sites: Inter-site synchrony is predominantly dependent on GABAergic ouput by parvalbumin-positive interneurons (PVIs) and not affected by challenges to the glutamatergic system. Using optogenetic interventions, we finally observe that inter-site synchrony inversely scales with the cellular excitability of PVIs. In conclusion, we identify the inter-site synchronization of ripple oscillations as a distinct function of PVI GABAergic output in states of rest, which may support the understanding of network dysregulation in states of disease.