Sound Localization in Preweanling Mice Was More Severely Affected by Deleting the Kcna1 Gene Compared to Deleting Kcna2, and a Curious Inverted-U Course of Development That Appeared to Exceed Adult Performance Was Observed in All Groups
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The submillisecond acuity for detecting rapid spatial and temporal fluctuations in acoustic stimuli observed in humans and laboratory animals depends in part on select groups of auditory neurons that preserve synchrony from the ears to the binaural nuclei in the brainstem. These fibers have specialized synapses and axons that use a low-threshold voltage-activated outward current, IKL, conducted through Kv1 potassium ion channels. These are in turn coupled with HCN channels that express a mixed cation inward mixed current, IH, to support precise synchronized firing. The behavioral evidence is that their respective Kcna1 or HCN1 genes are absent in adult mice; the results are weak startle reflexes, slow responding to noise offsets, and poor sound localization. The present behavioral experiments were motivated by an in vitro study reporting increased IKL in an auditory nucleus in Kcna2−/− mice lacking the Kv1.2 subunit, suggesting that Kcna2−/− mice might perform better than Kcna2+/+ mice. Because Kcna2−/− mice have only a 17–18-day lifespan, we compared both preweanling Kcna2−/− vs. Kcna2+/+ mice and Kcna1−/− vs. Kcna1+/+ mice at P12-P17/18; then, the remaining mice were tested at P23/P25. Both null mutant strains had a stunted physique, but the Kcna1−/− mice had severe behavioral deficits while those in Kcna2−/− mice were relatively few and minor. The in vitro increase of IKL could have resulted from Kv1.1 subunits substituting for Kv1.2 units and the loss of the inhibitory “managerial” effect of Kv1.2 on Kv1.1. However, any increased neuronal synchronicity that accompanies increased IKL may not have been enough to affect behavior. All mice performed unusually well on the early spatial tests, but then, they fell towards adult levels. This unexpected effect may reflect a shift from summated independent monaural pathways to integrated binaural processing, as has been suggested for similar observations for human infants.
KeywordsDeletion Kv1 subunits acoustic startle reflex noise offset sound localization
We thank Carol Robbins for her helpful comments and advice and Martha Zettel, John Housel and Linda Robinson for colony management.
This research was supported by USPHS NIH-NIA Grant AG09524, NIH-NIDCD Grants DC005409, DC004661, and DC002739 and by the Schmitt Foundation for Integrative Brain Research.
Compliance with Ethical Standards
All protocols were approved by the IACUCs of the Universities of Washington and Rochester and were in accord with USPHS regulations and the Federal Animal Welfare Act.
Conflict of Interest
The authors declare that they have no conflict of interest.
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