Economo, M. N., Martínez, J. J. & White, J. A. Membrane potential-dependent integration of synaptic inputs in entorhinal stellate neurons. Hippocampus 24, 1493–1505 (2014).

Stellate cells (SCs) of the medial entorhinal cortex exhibit robust spontaneous membrane-potential oscillations (MPOs) in the theta (4–12 Hz) frequency band as well as theta-frequency resonance in their membrane impedance spectra. Past experimental and modeling work suggests that these features may contribute to the phase-locking of SCs to the entorhinal theta rhythm and may be important for forming the hexagonally tiled grid cell place fields exhibited by these neurons in vivo. Among the major biophysical mechanisms contributing to MPOs is a population of persistent (non-inactivating or slowly inactivating) sodium channels. The resulting persistent sodium conductance (GNaP) gives rise to an apparent increase in input resistance as the cell approaches threshold. In this study, we used dynamic clamp to test the hypothesis that this increased input resistance gives rise to voltage-dependent, and thus MPO phase-dependent, changes in the amplitude of excitatory and inhibitory post-synaptic potential (PSP) amplitudes. We find that PSP amplitude depends on membrane potential, exhibiting a 5–10% increase in amplitude per mV depolarization. The effect is larger than—and sums quasi-linearly with—the effect of the synaptic driving force, V - Esyn. Given that input-driven MPOs 10 mV in amplitude are commonly observed in MEC stellate cells in vivo, this voltage- and phase-dependent synaptic gain is large enough to modulate PSP amplitude by over 50% during theta-frequency MPOs. Phase-dependent synaptic gain may therefore impact the phase locking and phase precession of grid cells in vivo to ongoing network oscillations. © 2014 Wiley Periodicals, Inc.