Reciprocal interactions between CA1 pyramidal and axo-axonic cells control sharp wave-ripple events

Excitation and inhibition compete to organize spike timing of pyramidal cells (PYR) in CA1 during network events, including sharp wave-ripples (SPW-R). Specific cellular-synaptic sources of inhibition in SPW-R remain unclear, as there are >60 types of GABAergic interneurons in CA1. Axo-axonic cells (AAC) are defined by their synaptic targeting of the axon initial segment of pyramidal cells, potently controlling spike output. The impact of AAC activity on SPW-R is controversial, due mainly to ambiguity of AAC identification. Here we monitored and manipulated opto-tagged AACs in behaving mice using silicon probe recordings. We found a large variability of AAC neurons, varying from enhanced to suppressed spiking during SPW-Rs, in contrast to the near-uniform excitation of other parvalbumin-expressing interneurons. AACs received convergent monosynaptic inputs from local pyramidal cell assemblies, which strongly influenced their participation in SPW-Rs. Optogenetic silencing of AACs increased power and duration of SPW-Rs, recruiting a greater number of PYR, suggesting AACs control SPW-R dynamics. We hypothesize that lateral inhibition by reciprocal PYR-AAC interactions thus supports the organization of cell assemblies in SPW-R.