The Role Of Hyperpolarization-Activated Cationic Current In Spike-Time Precision And Intrinsic Resonance In Cortical Neurons In Vitro

Hyperpolarization-activated cyclic nucleotide modulated current (I-h) sets resonance frequency within the theta-range (5-12 Hz) in pyramidal neurons. However, its precise contribution to the temporal fidelity of spike generation in response to stimulation of excitatory or inhibitory synapses remains unclear. In conditions where pharmacological blockade of I-h does not affect synaptic transmission, we show that postsynaptic h-channels improve spike time precision in CA1 pyramidal neurons through two main mechanisms. I-h enhances precision of excitatory postsynaptic potential (EPSP)-spike coupling because I-h reduces peak EPSP duration. I-h improves the precision of rebound spiking following inhibitory postsynaptic potentials (IPSPs) in CA1 pyramidal neurons and sets pacemaker activity in stratum oriens interneurons because I-h accelerates the decay of both IPSPs and after-hyperpolarizing potentials (AHPs). The contribution of h-channels to intrinsic resonance and EPSP waveform was comparatively much smaller in CA3 pyramidal neurons. Our results indicate that the elementary mechanisms by which postsynaptic h-channels control fidelity of spike timing at the scale of individual neurons may account for the decreased theta-activity observed in hippocampal and neocortical networks when h-channel activity is pharmacologically reduced.