Fig. 2. HCN channels regulate intracellular and extracellular voltage responses to theta frequency inputs.
(A) Voltage response of a passive neuronal compartment (top) and of a neuronal compartment expressing HCN channels (bottom) to a theta-frequency sinusoidal current injection (black traces) for 1 s. Notice that the passive voltage response shows a phase lag with respect to the input current and a reduction in amplitude while the voltage response in the presence of HCN channels shows a corresponding phase lead (Narayanan and Johnston, 2008). (B) Left top: A chirp stimulus, constant amplitude sinusoidal current linearly increasing in frequency from 0 to 20 Hz in 20 s. Left middle: Passive voltage response to the chirp stimulus showing low-pass filtering. Left bottom: Voltage response in the presence of HCN channels showing a band-pass response with the highest amplitude at its resonance frequency (fR). Right: Illustrative impedance amplitude profiles show a low-pass response for the passive compartment and a band-pass response in the presence of HCN channels, with fR in the theta-band. Such low-pass and band-pass responses are also reflected in the LFP power spectral density in the absence and presence of HCN channels, respectively (see (Ness et al., 2016, 2018)) (C) Left: A morphologically realistic CA1 pyramidal neuron model representing a population of neurons in a cylindrical neuropil, with inhibitory synapses targeting the perisomatic regions and excitatory synapses targeting the dendrites in the SR. An experimentally constrained HCN channel gradient was introduced in the model accounting for an increase in HCN conductance (gh) with distance from the soma. A single electrode with seven recording sites, located at the center of the cylindrical neuropil spanned all strata of the CA1. Right: Lead in the LFP phase introduced by the presence of HCN channels increases with HCN conductance along the somato-apical axis ((Sinha and Narayanan, 2015); *: p < 0.05; **: p < 0.005; Wilcoxon signed rank test). (D) Top: Raster plots for 25 passive model neurons with low spike-phase coherence with respect to theta frequency LFP. Middle: Same as top but with a gradient of HCN channels introduced in the model shows enhancement of spike-phase coherence and spike theta-phase preference. Bottom: Same as middle but illustrating the impact of bidirectional HCN plasticity on reconfiguration of cell assemblies. SP: stratum pyramidale, SR: stratum radiatum, SLM: stratum lacunosum moleculare.