Hyperpolarization-activated cyclic nucleotide-gated channels in olfactory sensory neurons regulate axon extension and glomerular formation.
Hyperpolarization-activated cyclic nucleotide-gated channels in olfactory sensory neurons regulate axon extension and glomerular formation.
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DOI：
10.1523/jneurosci.4225-10.2010
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发表时间：
2010-12-08
期刊：
影响因子：
--
通讯作者：
Greer CA
中科院分区：
文献类型：
--
作者：
Mobley AS;Miller AM;Araneda RC;Maurer LR;Müller F;Greer CA
Mechanisms influencing the development of olfactory bulb glomeruli are poorly understood. While odor receptors (OR) play an important role in olfactory sensory neuron (OSN) axon targeting/coalescence (;;), recent work showed that G-protein activation alone is sufficient to induce OSN axon coalescence suggesting an activity-dependent mechanism in glomerular development. Consistent with these data, OSN axon projections and convergence are perturbed in mice deficient for adenylyl cyclase III, which is downstream from the OR and catalyzes the conversion of ATP to cAMP. However, in cyclic-nucleotide-gated (CNG) channel knockout mice OSN axons are only transiently perturbed, suggesting that the CNG channel may not be the sole target of cAMP. This prompted us to investigate an alternative channel, the hyperpolarization-activated, cyclic nucleotide-gated cation channel (HCN), as a potential developmental target of cAMP in OSNs. Here, we demonstrate that HCN channels are developmentally precocious in OSNs and therefore are plausible candidates for affecting OSN axon development. Inhibition of HCN channels in dissociated OSNs significantly reduced neurite outgrowth. Moreover, in HCN1 knockout mice the formation of glomeruli was delayed in parallel with perturbations of axon organization in the olfactory nerve. These data support the hypothesis that the outgrowth and coalescence of OSN axons is, at least in part, subject to activity-dependent mechanisms mediated via HCN channels.
