Theta resonance and synaptic modulation scale activity patterns in the medial entorhinal cortex stellate cells

Stellate cells (SCs) of the medial entorhinal cortex (MEC) are rich in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are known to effectively shape their activity patterns. The explanatory mechanisms, however, have remained elusive. One important but previously unassessed possibility is that HCN channels control the gain of synaptic inputs to these cells. Here, we test this possibility in rat brain slices, while subjecting SCs to a stochastic synaptic bombardment using the dynamic clamp. We show that in the presence of synaptic noise, HCN channels mainly exert their influence by increasing the relative signal gain in the theta frequency through the theta modulation of stochastic synaptic inputs. This subthreshold synaptic modulation then translates into a spiking resonance, which steepens with excitation in the presence of HCN channels. We present here a systematic assessment of synaptic theta modulation and trace its implications to the suprathreshold control of firing rate motifs. Such analysis was yet lacking in the SC literature. Furthermore, we assess the impact of noise statistics on this gain modulation and indicate possible mechanisms for the emergence of membrane theta oscillations and synaptic ramps, as observed in vivo. We support the data with a computational model that further unveils a competing role of inhibition, suggesting important implications for MEC computations.