Dorsal–ventral organization of theta‐like activity intrinsic to entorhinal stellate neurons is mediated by differences in stochastic current fluctuations

Non‐technical summary Navigation by mammals relies on neurons in the brain that encode location, but the mechanisms involved are not understood. Some theories propose critical roles for oscillations generated intrinsically by location‐encoding neurons. Correlations between the frequency of intrinsic activity and the resolution of location encoding support this idea. However, other evidence suggests that cellular mechanisms thought to set the frequency of intrinsic activity may instead primarily function to tune neuronal responses to synaptic input. This study provides evidence that activity intrinsic to location‐encoding neurons is explained by random opening and closing of neuronal ion channels and is not consistent with oscillator theories. The correlation between intrinsic frequency fluctuations and resolution of spatial encoding is explained by differences in the density of ion channels that account for tuning of synaptic responses. These results point towards the importance of synaptic response tuning for encoding of spatial location. The membrane potential dynamics of stellate neurons in layer II of the medial entorhinal cortex are important for neural encoding of location. Previous studies suggest that these neurons generate intrinsic theta‐frequency membrane potential oscillations, with a period that depends on neuronal location on the dorsal–ventral axis of the medial entorhinal cortex, and which in behaving animals could support generation of grid‐like spatial firing fields. To address the nature and organization of this theta‐like activity, we adopt the Lomb method of least‐squares spectral analysis. We demonstrate that peaks in frequency spectra that differ significantly from Gaussian noise do not necessarily imply the existence of a periodic oscillator, but can instead arise from filtered stochastic noise or a stochastic random walk. We show that theta‐like membrane potential activity recorded from stellate neurons in mature brain slices is consistent with stochastic mechanisms, but not with generation by a periodic oscillator. The dorsal–ventral organization of intrinsic theta‐like membrane potential activity, and the modification of this activity during block of HCN channels, both reflect altered frequency distributions of stochastic spectral peaks, rather than tuning of a periodic oscillator. Our results demonstrate the importance of distinguishing periodic oscillations from stochastic processes. We suggest that dorsal–ventral tuning of