Rhythm, resonance and reliability in oscillatory stellate cells of the entorhinal cortex

The parahippocampal region is well known as a formation central to the neural processes of learning and memory. Within this region, the entorhinal cortex (EC) acts as an ‘information gate’, channeling multimodal information from the neocortex both into and out of the hippocampus proper. The majority of principal neurons of the EC superficial layers are spiny stellate cells (SCs), which collect input from the neocortex, and whose axons deliver the perforant path input to the hippocampus. SCs are easily distinguished in intracellular electrophysiological recordings: in response to moderate injections of DC currents, they exhibit subthreshold membrane potential oscillations at frequencies in the theta (3–12 Hz) range. Larger injections of DC currents elicit spikes, phase-locked to the frequency of the subthreshold oscillations.; During memory formation, synchronized patterns of electrical activity across the EC and other hippocampal areas give rise to a low-frequency rhythmic pattern, easily detected by EEG measurement and known as the theta rhythm. Because of their intrinsically rhythmic membrane properties, SCs are hypothesized to contribute to the generation of the population theta rhythm in the EC. Further, because the SCs are the cells responsible for the majority of the input to the hippocampus, they are an important and natural focus for investigation into the mechanisms by which neural inputs are transformed in successive stages of processing within the brain.; This work focuses on how intrinsic cellular rhythmicity in SCs influences their responses to inputs of different frequency content. First, we show that SCs exhibit a classical resonance to sinusoidal inputs in the subthreshold regime. Second, we show that SCs spike more reliably to inputs with frequency content biased towards the theta range; we also show that the enhanced reliability is, surprisingly, not the result of a simple linear subthreshold resonance to those inputs. Third, we show that the slow, mixed-cation current I _h is responsible for subthreshold SC resonance, and contributes to the enhanced SC reliability to theta-rich stimuli. However, SCs still exhibit other traits of rhythmicity, under I_h blockade. Fourth, using a generalized form of principal component analysis and information theory, we show that SCs select particular features with consistent temporal signatures from a given type of stimulus. The selected mix of those features varies with input amplitude and frequency content Together, these results show that SCs express multiple mechanisms that contribute to intrinsic rhythmicity, and that these mechanisms allow SCs to tailor their response to different stimulus conditions.