E-Cannula reveals anatomical diversity in sharp-wave ripples as a driver for the recruitment of distinct hippocampal assemblies

Abstract

The hippocampus plays a critical role in spatial navigation and episodic memory. However, research on in vivo hippocampal activity dynamics has mostly relied on single modalities such as electrical recordings or optical imaging, with respectively limited spatial and temporal resolution. This technical difficulty greatly impedes multi-level investigations into network state-related changes in cellular activity. To overcome these limitations, we developed the E-Cannula integrating fully transparent graphene microelectrodes with imaging-cannula. The E-Cannula enables the simultaneous electrical recording and two-photon calcium imaging from the exact same population of neurons across an anatomically extended region of the mouse hippocampal CA1 stably across several days. These large-scale simultaneous optical and electrical recordings showed that local hippocampal sharp wave ripples (SWRs) are associated with synchronous calcium events involving large neural populations in CA1. We show that SWRs exhibit spatiotemporal wave patterns along multiple axes in 2D space with different spatial extents (local or global) and temporal propagation modes (stationary or travelling). Notably, distinct SWR wave patterns were associated with, and decoded from, the selective recruitment of orthogonal CA1 cell assemblies. These results suggest that the diversity in the anatomical progression of SWRs may serve as a mechanism for the selective activation of the unique hippocampal cell assemblies extensively implicated in the encoding of distinct memories. Through these results we demonstrate the utility of the E-Cannula as a versatile neurotechnology with the potential for future integration with other optical components such as green lenses, fibers or prisms enabling the multi-modal investigation of cross-time scale population-level neural dynamics across brain regions.