h channel-dependent deficit of theta oscillation resonance and phase shift in temporal lobe epilepsy

I_h tunes hippocampal CA1 pyramidal cell dendrites to optimally respond to theta inputs (4–12 Hz), and provides a negative time delay to theta inputs. Decreased I_h activity, as seen in experimental temporal lobe epilepsy (TLE), could significantly alter the response of dendrites to theta inputs. Here we report a progressive erosion of theta resonance and phase lead in pyramidal cell dendrites during epileptogenesis in a rat model of TLE. These alterations were due to decreased I_h availability, via a decline in HCN1/HCN2 subunit expression resulting in decreased h currents, and altered kinetics of the residual channels. This acquired HCN channelopathy thus compromises temporal coding and tuning to theta inputs in pyramidal cell dendrites. Decreased theta resonance in vitro also correlated with a reduction in theta frequency and power in vivo. We suggest that the neuronal/circuitry changes associated with TLE, including altered I_h-dependent inductive mechanisms, can disrupt hippocampal theta function.