title: HCN channels enhance spike phase coherence and regulate the phase of spikes and LFPs in the theta-frequency range.
abstract: What are the implications for the existence of subthreshold ion channels, their localization profiles, and plasticity on local field potentials (LFPs)? Here, we assessed the role of hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels in altering hippocampal theta-frequency LFPs and the associated spike phase. We presented spatiotemporally randomized, balanced theta-modulated excitatory and inhibitory inputs to somatically aligned, morphologically realistic pyramidal neuron models spread across a cylindrical neuropil. We computed LFPs from seven electrode sites and found that the insertion of an experimentally constrained HCN-conductance gradient into these neurons introduced a location-dependent lead in the LFP phase without significantly altering its amplitude. Further, neurons fired action potentials at a specific theta phase of the LFP, and the insertion of HCN channels introduced large lags in this spike phase and a striking enhancement in neuronal spike-phase coherence. Importantly, graded changes in either HCN conductance or its half-maximal activation voltage resulted in graded changes in LFP and spike phases. Our conclusions on the impact of HCN channels on LFPs and spike phase were invariant to changes in neuropil size, to morphological heterogeneity, to excitatory or inhibitory synaptic scaling, and to shifts in the onset phase of inhibitory inputs. Finally, we selectively abolished the inductive lead in the impedance phase introduced by HCN channels without altering neuronal excitability and found that this inductive phase lead contributed significantly to changes in LFP and spike phase. Our results uncover specific roles for HCN channels and their plasticity in phase-coding schemas and in the formation and dynamic reconfiguration of neuronal cell assemblies.
authors: Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
authors: Manisha
authors: M
authors: Sinha
authors: Cellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India rishi@mbu.iisc.ernet.in.
authors: Rishikesh
authors: http://orcid.org/0000-0002-1362-4635
authors: R
authors: Narayanan
mesh_terms: D000818:Animals; D003198:Computer Simulation; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D013826:Theta Rhythm / Q000502:physiology*
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
keywords: active dendrites; channel localization; local field potential; neuronal inductor; phase coding