Expression and Localization of Kv1.1 and Kv3.1b Potassium Channels in the Cochlear Nucleus and Inferior Colliculus after Long-Term Auditory Deafferentation.

Marianny Pernia,Clara Poveda,Juan Alvarado,Miguel Merchan,David Ryugo,Maria Valero,Jose Juiz

doi:10.3390/brainsci10010035

Marianny Pernia, Clara Poveda + Show 5 more

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https://doi.org/10.3390/brainsci10010035

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Abstract

Deafness affects the expression and distribution of voltage-dependent potassium channels (Kvs) of central auditory neurons in the short-term, i.e., hours to days, but the consequences in the expression of Kvs after long-term deafness remain unknown. We tested expression and distribution of Kv1.1 and Kv3.1b, key for auditory processing, in the rat cochlear nucleus (CN), and in the inferior colliculus (IC), at 1, 15 and 90 days after mechanical lesion of the cochlea, using a combination of qRT-PCR and Western blot in the whole CN, along with semi-quantitative immunocytochemistry in the AVCN, where the role of both Kvs in the control of excitability for accurate auditory timing signal processing is well established. Neither Kv1.1/Kv3.1b mRNA or protein expression changed significantly in the CN between 1 and 15 days after deafness. At 90 days post-lesion, however, mRNA and protein expression for both Kvs increased, suggesting that regulation of Kv1.1 and Kv3.1b expression is part of cellular mechanisms for long-term adaptation to auditory deprivation in the CN. Consistent with these findings, immunocytochemistry showed increased labeling intensity for both Kvs in the AVCN at day 90 after cochlear lesion. This increase argues that up-regulation of Kv1.1 and Kv3.1b in AVCN neurons may be required to adapt intrinsic excitability to altered input over the long term after auditory deprivation. Contrary to these findings in the CN, expression levels of Kv1.1 and Kv3.1b in the IC did not undergo major changes after cochlear lesion. In particular, there was no evidence of long-term up-regulation of either Kv1.1 or Kv3.1b, supporting that such post-lesion adaptive mechanism may not be needed in the IC. These results reveal that post-lesion adaptations do not necessarily involve stereotyped plastic mechanisms along the entire auditory pathway.

Highlights

Neurons in brain stem auditory nuclei, in particular those involved in processing timing cues in the cochlear nucleus (CN) and the inferior colliculus (IC), express two voltage-dependent potassium channel subunits (Kv) designated as Kv1.1 and Kv3.1b according to their gene lineage [1,2,3,4,5,6]
We report that mechanical damage to the auditory receptor in the rat, with subsequent interruption of evoked auditory activity, results, in the long term, i.e., 90 days after cochlear lesion, in overall increased Kv1.1 and Kv3.1b gene and protein expression in the CN, as shown by RT-qPCR and Western blot
We show that in the rat, at day 1 after the cochlear lesion, Kv1.1 and Kv3.1b expression and localization in the anteroventral division of the CN (AVCN) do not differ from normall hearing animals, suggesting that immediate changes in the expression of these two Kvs after deafness, if present, recover quickly at different rates than previously reported in a chick model, at least in the case of Kv1.1 [21]

Summary

Introduction

Neurons in brain stem auditory nuclei, in particular those involved in processing timing cues in the cochlear nucleus (CN) and the inferior colliculus (IC), express two voltage-dependent potassium channel subunits (Kv) designated as Kv1.1 and Kv3.1b according to their gene lineage [1,2,3,4,5,6]. Kv3.1b activates at higher voltages and deactivates quickly, contributing to the generation of short action potentials for rapid firing. Both mechanisms seem to be closely related to processing for acoustic timing. In the IC, which receives massively converging ascending input from more caudal auditory nuclei [11], presence of Kvs [2,6,12]

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