Propagation of sharp wave-ripple activity in the mouse hippocampal CA3 subfield in vitro

Natalie Schieferstein, Ana del Toro, Roberta Evangelista, Barbara Imbrosci, Aarti Swaminathan, Dietmar Schmitz, Nikolaus Maier, Richard Kempter

Sharp wave-ripple complexes (SPW-Rs) are spontaneous oscillatory events that characterize hippocampal activity during resting periods and slow-wave sleep. SPW-Rs are related to memory consolidation – the process during which newly acquired memories are transformed into long-lasting memory traces. To test the involvement of SPW-Rs in this process, it is crucial to understand how SPW-Rs originate and propagate throughout the hippocampus. SPW-Rs can originate in CA3, and they typically spread from CA3 to CA1, but little is known about their formation within CA3. To investigate the generation and propagation of SPW-Rs in CA3, we recorded from mouse hippocampal slices using multi-electrode arrays and patch-clamp electrodes. We characterized extracellular and intracellular correlates of SPW-Rs and quantified their propagation along the pyramidal cell layer of CA3. We found that a hippocampal slice can be described by a speed and a direction of propagation of SPW-Rs. The preferred propagation direction was from CA3c (the subfield closer to the dentate gyrus) toward CA3a (the subfield at the boundary to CA2). In patch-clamp recordings from CA3 pyramidal neurons, propagation was estimated separately for excitatory and inhibitory currents associated with SPW-Rs. We found that propagation speed and direction of excitatory and inhibitory currents were correlated. The magnitude of the speed of propagation of SPW-Rs within CA3 was consistent with the speed of propagation of action potentials in axons of CA3 principal cells.

J Physiol. 602(19):5039-5059 (2024)

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