TY - JOUR T1 - Theta oscillations gate the transmission of reliable sequences in the medial entorhinal cortex JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0059-20.2021 SP - ENEURO.0059-20.2021 AU - Arun Neru AU - Collins Assisi Y1 - 2021/04/02 UR - http://www.eneuro.org/content/early/2021/04/01/ENEURO.0059-20.2021.abstract N2 - Stability and precision of sequential activity in the entorhinal cortex 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 entorhinal cortex (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, due to 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.Significance statementThe theta rhythm is a prominent oscillation in the brain and known to play a role in different forms of learning and memory, for its association with movement and its disruption in some pathologies. Oscillations in general, and theta in particular, are thought to coordinate the activity of distributed brain regions. Our study provides a mechanistic understanding of the role of theta oscillations in the generation of stable sequences of activity and its transmission across brain regions. We model a specific microcircuit (stellate cells coupled via inhibitory interneurons) based on the known architecture of the MEC. This circuit motif occurs across various brain regions. Thus, mechanisms of spatiotemporal patterning observed in the MEC are recapitulated in other circuits as well. ER -