Differential expression of hyperpolarization-activated cyclic nucleotide-gated channel subunits during hippocampal development in the mouse.

Hyunhyo Seo,Myoung-Jin Seol,Kyungmin Lee

doi:10.1186/s13041-015-0103-4

Abstract

BackgroundHyperpolarization-activated cyclic nucleotide-gated (HCN) channels help control the rhythmic activation of pacemaker neurons during brain development. However, little is known about the timing and cell type specificity of the expression of HCN isoforms during development of the hippocampus.ResultsHere we examined the developmental expression of the brain-enriched HCN1, HCN2, and HCN4 isoforms of HCN channels in mouse hippocampus from embryonic to postnatal stages. All these isoforms were expressed abundantly in the hippocampus at embryonic day 14.5 and postnatal day 0. Each HCN channel isoform showed subfield-specific expression within the hippocampus from postnatal day 7, and only HCN4 was found in glial cells in the stratum lacunosum moleculare at this developmental stage. At postnatal days 21 and 56, all HCN isoforms were strongly expressed in the stratum lacunosum moleculare and the stratum pyramidale of the Cornu Ammonis (CA), as well as in the hilus of the dentate gyrus, but not in the subgranular zone. Furthermore, the immunolabeling for all these isoforms was colocalized with parvalbumin immunolabeling in interneurons of the CA field and in the dentate gyrus.ConclusionsOur mapping data showing the temporal and spatial changes in the expression of HCN channels suggest that HCN1, HCN2, and HCN4 subunits may have distinct physiological roles in the developing hippocampus.

Highlights

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels help control the rhythmic activation of pacemaker neurons during brain development
Hippocampal expression of HCN channel subunits in the brain of E14.5 embryos The hippocampus originates from the dorsomedial telencephalon, which commences its invagination to build the medial walls of the telencephalic hemispheres at approximately E11 in the mouse
We investigated the expression of HCN channel subunits in the brain of E14.5 embryos

Summary

Introduction

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels help control the rhythmic activation of pacemaker neurons during brain development. HCN channels are observed in dendrites [3,4], and in presynaptic axon terminals [5,6], where they have a role in regulating synaptic transmission [3,4] These channels conduct a hyperpolarizationactivated cation current (Ih), which plays a key role in the pacemaker depolarization that generates rhythmic activity, and mediates a variety of neural functions [7]. The properties of these currents passing through the HCN channels affect membrane excitability and the synchronized activity of neurons [8,9]. The biophysical diversity of HCN channels suggests that differential gene expression and assemblage of the HCN subunits may produce the heterogeneity observed in Ih currents [17]

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Conclusion