Theta Oscillations Gate the Transmission of Reliable Sequences in the Medial Entorhinal Cortex

Stability and precision of sequential activity in the entorhinal cortex (EC) is crucial for encoding spatially guided behavior and memory. These sequences are driven by constantly evolving sensory inputs and persist despite a noisy background. In a realistic computational model of a medial EC (MEC) microcircuit, we show that intrinsic neuronal properties and network mechanisms interact with theta oscillations to generate reliable outputs. In our model, sensory inputs activate interneurons near their most excitable phase during each theta cycle. As the inputs change, different interneurons are recruited and postsynaptic stellate cells are released from inhibition. This causes a sequence of rebound spikes. The rebound time scale of stellate cells, because of an h-current, matches that of theta oscillations. This fortuitous similarity of time scales ensures that stellate spikes get relegated to the least excitable phase of theta and the network encodes the external drive but ignores recurrent excitation. In contrast, in the absence of theta, rebound spikes compete with external inputs and disrupt the sequence that follows. Further, the same mechanism where theta modulates the gain of incoming inputs, can be used to select between competing inputs to create transient functionally connected networks. Our results concur with experimental data that show, subduing theta oscillations disrupts the spatial periodicity of grid cell receptive fields. In the bat MEC where grid cell receptive fields persist even in the absence of continuous theta oscillations, we argue that other low frequency fluctuations play the role of theta.