Hippocampal sharp-wave ripples and their spike assembly content are regulated by the medial entorhinal cortex

Hippocampal sharp-wave ripples (SPW-Rs) are critical for memory consolidation and retrieval. The neuronal content of spiking during SPW-Rs is believed to be under the influence of neocortical inputs via the entorhinal cortex (EC). Optogenetic silencing of the medial EC (mEC) reduced the incidence of SPW-Rs with minor impacts on their magnitude or duration, similar to local CA1 silencing. The effect of mEC silencing on CA1 firing and field potentials was comparable to the effect of transient cortex-wide DOWN states of non-REM (NREM) sleep, implying that decreased SPW-R incidence in both cases is due to tonic disfacilitation of hippocampal circuits. The neuronal composition of CA1 pyramidal neurons during SPW-Rs was altered by mEC silencing but was restored immediately after silencing. We suggest that the mEC provides both tonic and transient influences on hippocampal network states by timing the occurrence of SPW-Rs and altering their neuronal content.