期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：17
页码：E2207-E2216
DOI：10.1073/pnas.1419017112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe impact of the pacemaking hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels on local field potentials (LFP) has not been analyzed. Here, employing a neuropil of several morphologically precise hippocampal neuronal models that received systematically randomized rhythmic synaptic inputs, we demonstrate that HCN channels alter the phase, but not the amplitude, of LFPs. Further, it is known that the spike timings of individual neurons follow the beat of the LFPs and fire at precise phases of the LFP beat. We demonstrate that the presence of HCN channels alters this phase and enhances the precision to which the spikes follow the LFP beat. These results unveil several important roles for HCN channels, extending their regulatory potential beyond single-neuron physiology. 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.
关键词：active dendrites ; local field potential ; neuronal inductor ; phase coding ; channel localization
