IMPLICATION OF ASTROCYTES IN HIPPOCAMPAL NETWORK EXCITABILITY AND SHARP WAVE-RIPPLE ACTIVITY

The hippocampus is a key brain structure involved in learning and memory. Within the hippocampus, high-frequency oscillations known as sharp wave–ripples (SWRs) occur, which are thought to serve the transfer of memory-related content from the hippocampus to the neocortex. While memory consolidation has traditionally been attributed to neuronal activity, recent research has highlighted a potential role of astrocytes in modulating this process, for instance via gliotransmission. To investigate whether astrocytes correlate with and may actively contribute to SWR generation, we have developed an in vitro system to perform simultaneous electrophysiology and wide-field calcium imaging in acute hippocampal slices with spontaneously occurring SWRs. Measurements of astrocytic population calcium signal using virally expressed GCaMP8m suggest temporal coupling of astrocytic calcium increases and SWRs. Furthermore, increases in astrocytic calcium signal were positively correlated with the amplitude of ripples. In addition, this in vitro approach allowed us to use chemo- and optogenetic tools to interfere with molecular mechanisms. Optogenetic inhibition of astrocytes via ArchT reduced SWR event frequency and amplitude. Additionally, chemogenetic manipulation of the astrocytic population using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) appeared to affect SWR amplitude and event occurrence. Our findings suggest that astrocytes may critically contribute to the regulation of high-frequency network events in the hippocampus and that disruption of their normal function can compromise synchronous population events such as SWRs within hippocampal circuits.