Patterned activation of hippocampal network (approximately 10 Hz) during in vitro sharp wave-ripples

Sharp waves (SPWs) are endogenous hippocampal network activity that occurs during certain behaviors and it is thought to be involved in the process of memory consolidation. Frequently, SPWs are generated in bursts or clusters of several consecutive events forming discrete episodes of activity, a hitherto unexplored feature of this prominent hippocampal network activity. In the present study, using rat ventral hippocampal slices, we show that clusters of SPWs consist of two to four consecutive events occurring at a frequency of approximately 10 Hz (range, 7-14 Hz). Similarly to the first (primary) event in a cluster the following (secondary) SPWs correspond to inhibitory postsynaptic potentials in CA1 pyramidal cells. Furthermore, the initiation of secondary SPWs in the 23% of cells coincides with postinhibitory rebound excitation. Antagonists of NMDA receptors reversibly abolish secondary but not primary SPWs suggesting that their generation depend on the activation of NMDA receptors. Furthermore, the generation of clusters of SPWs is very sensitive to moderate pharmacological reduction or enhancement of the GABA (A) receptor-mediated transmission suggesting that precise levels of GABAergic transmission are required for the clustered generation of SPWs. In addition, enhancement of GABA (A) receptor-mediated transmission affects the timing of secondary SPWs initiation. Trains of high-frequency (100 Hz) or theta burst stimulation at the Schaffer collaterals that induce long-term potentiation of the evoked field response enhance the incidence of SPWs' clusters and the amplitude of the primary SPWs. We propose that sequential approximately 10 Hz clustered activation of the local hippocampal circuit occurring under the dynamics of SPWs and depending on NMDA receptors and an accurate level of GABAergic synaptic transmission is an essential pattern of precisely controlled network activity involved in synaptic plasticity processes with potential implications in mnemonic functions.