Cellular mechanisms of entorhinal cortex spontaneous and navigation-related grid cell oscillations

Intracellular recordings of grid cells have been previously obtained from principal neurons in the superficial medial entorhinal cortex (MEC) of behaving head-fixed mice. These recordings indicate that action potentials occur on the depolarizing phases of intracellular slow oscillations. Here we use network simulations and <i>in vitro</i> experiments to investigate the hypothesis that slow grid cell oscillations <i>in vivo</i> have cellular mechanisms similar to those of spontaneous slow wave oscillations (SWO) in drug-free entorhinal cortex (EC) slices. Simulations suggest that electrical coupling plays a vital role in oscillation genesis; slice experiments demonstrating spikelets in entorhinal cortex SWO are consistent. We reviewed previously published (by others) <i>in vivo</i> grid cell recordings and found spikelets to be present in entorhinal principal neurons. The data suggest that afferent inputs to entorhinal cortex during exploration influence the period and phase of grid cell oscillations, but may not be necessary for the oscillations themselves; while both chemical and electrical synaptic coupling <i>within</i> the entorhinal cortex give the oscillation its special characteristics. Importantly, spikelets are not only interesting in themselves, but imply the existence of pyramidal cell electrical coupling which may help to create local modules of grid cells having similar periods, spatial phases, and orientation.