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 (IKir). In this work, we tested whether other subthreshold conductances vary homeostatically to maintain membrane excitability constant across the two subtypes. We found that Ih expression covaries specifically with IKir in order to maintain membrane resistance constant. The impact of Ih on membrane resistance is dependent on the level of IKir expression, being much smaller in quiet neurons with bigger IKir, but Ih 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.
Highlights
Theoretical and experimental evidence suggests that the expression levels of different ion channels and conductances vary across individual neurons with similar firing properties (Prinz et al, 2004; Marder and Goaillard, 2006; Goaillard et al, 2009), showing that similar firing properties can be achieved by different combinations of ion channel densities
We studied the principal neuron of the dorsal cochlear nucleus (DCN) (Zhang and Oertel, 1994), the fusiform neuron
Fusiform Neurons Express a More Robust Ih in Active than in Quiet Neurons. Consistent with this hypothesis, we found that active neurons show bigger hyperpolarization sag of the membrane potential. Because this sag is inhibited by the hyperpolarization-activated cationic current (Ih) antagonist ZD7288, this suggests the presence of a bigger Ih in these neurons that may normalize the input resistance of quiet and active neurons
Summary
Theoretical and experimental evidence suggests that the expression levels of different ion channels and conductances vary across individual neurons with similar firing properties (Prinz et al, 2004; Marder and Goaillard, 2006; Goaillard et al, 2009), showing that similar firing properties can be achieved by different combinations of ion channel densities. If the levels of different conductances in a neuron follow specific rules to maintain stable electrophysiological properties or the neuron can attain the same membrane characteristics using several combinations of densities of different ion channels is still a matter of debate. To address this question, we studied the principal neuron of the dorsal cochlear nucleus (DCN) (Zhang and Oertel, 1994), the fusiform neuron. We do not know how the other subthreshold conductances present in the DCN fusiform neuron affect the membrane properties of this neuron, if variations in their expression correlates with the firing mode and subthreshold membrane properties
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