I(h) Equalizes Membrane Input Resistance in a Heterogeneous Population of Fusiform Neurons in the Dorsal Cochlear Nucleus

I(h) 使背侧耳蜗核中梭状神经元异质群体的膜输入电阻趋于一致

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Abstract

In a neuronal population, several combinations of its ionic conductances are used to attain a specific firing phenotype. Some neurons present heterogeneity in their firing, generally produced by expression of a specific conductance, but how additional conductances vary along in order to homeostatically regulate membrane excitability is less known. Dorsal cochlear nucleus principal neurons, fusiform neurons, display heterogeneous spontaneous action potential activity and thus represent an appropriate model to study the role of different conductances in establishing firing heterogeneity. Particularly, fusiform neurons are divided into quiet, with no spontaneous firing, or active neurons, presenting spontaneous, regular firing. These modes are determined by the expression levels of an intrinsic membrane conductance, an inwardly rectifying potassium current (I(Kir)). In this work, we tested whether other subthreshold conductances vary homeostatically to maintain membrane excitability constant across the two subtypes. We found that I(h) expression covaries specifically with I(Kir) in order to maintain membrane resistance constant. The impact of I(h) on membrane resistance is dependent on the level of I(Kir) expression, being much smaller in quiet neurons with bigger I(Kir), but I(h) variations are not relevant for creating the quiet and active phenotypes. Finally, we demonstrate that the individual proportion of each conductance, and not their absolute conductance, is relevant for determining the neuronal firing mode. We conclude that in fusiform neurons the variations of their different subthreshold conductances are limited to specific conductances in order to create firing heterogeneity and maintain membrane homeostasis.

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