A possible role of ectopic action potentials in the in vitro hippocampal sharp wave–ripple complexes

Abstract

Sharp wave–ripple (SPW-R) complexes are physiological pattern of network activity in the hippocampus thought to play important role in memory consolidation. During SPW-R activity the excitability of both pyramidal cells and certain types of interneurons in the CA1 region is transiently increased. As a result pyramidal cells receive inhibitory input during network oscillation, yet a relatively small group of pyramidal cells transmit their output to CA1 targets. However, the exact nature of CA1 output during SPW-R activity is not clear. In this study, using simultaneous intracellular and field recordings from rat ventral hippocampal slices maintained at 32 °C and spontaneously generating SPW-R complexes we show that 20% of CA1 pyramidal cells fired putative ectopic action potentials (e-APs) phase-related to SPW-Rs. The highest probability of ectopic discharge occurred at the maximal amplitude of the ripple oscillation and always during the period of SPW-R-associated inhibitory postsynaptic potentials (IPSPs) in pyramidal cells. Both e-APs and IPSPs were abolished under blockade of GABAA receptor-mediated synaptic transmission by bicuculline. Ectopic APs phase-locked to SPW-R events were also evoked by Schaffer collateral stimulation subthreshold for and with longer latency than monosynaptic orthodromic APs. A fraction of CA1 pyramidal cells (25.7%), most of them distinct from the cells firing e-APs, fired orthodromic APs with highest probability before the onset of SPW-Rs. We hypothesize that putative ectopic spikes in pyramidal cells, presumably triggered by GABAergic synaptic mechanisms, by serving as output of the CA1 region might provide a reliable mechanism for optimized information transfer between hippocampus and its cortical targets during SPW-R activity. On the other hand, orthodromic APs might contribute to the initiation and synchronization of the population activity.