class="head no_bottom_margin" id="sec1title">IntroductionPrecise temporal coding of sound requires proper adjustment of ion channel expression in auditory neurons (). Two types of voltage-gated K+ (Kv) channels, Kv1.1 and Kv3.1, play central roles in the temporal coding. These channels mediate low- and high-voltage-activated K+ currents, respectively. Kv1.1 is activated strongly at subthreshold potential and improves phasic firing by suppressing aberrant spike generation during synaptic depolarization, whereas Kv3.1 accelerates falling phase of spikes and promotes firing at high frequency (, ).Avian nucleus magnocellularis (NM), a homolog of mammalian anteroventral cochlear nucleus, is involved in the temporal coding (, ) and well known for rich expression of these Kv channels (, , , ). NM neurons are tuned to a specific frequency of sound (characteristic frequency, CF), and arranged tonotopically within the nucleus such that neurons with high CF are located rostromedially (). Moreover, they are differentiated biophysically as well as morphologically along the tonotopic axis (, , , ). One prominent example is the differentiation of Kv1.1; the expression level of this channel increases in neurons with higher CF, which is considered crucial in adjusting neuronal excitability to the CF-specific patterns of afferent input in NM (). Recently, we reported that the differentiation of Kv1.1 was created because afferent input augmented the expression to a larger extent in higher-CF neurons (href="#bib1" rid="bib1" class=" bibr popnode">Akter et al., 2018), showing the importance of afferent input in setting the level of Kv1.1 expression. Intriguingly, however, the auditory threshold is higher for higher-frequency sound (href="#bib15" rid="bib15" class=" bibr popnode">Jones et al., 2006, href="#bib42" rid="bib42" class=" bibr popnode">Saunders et al., 1973), and therefore, the level of afferent input cannot solely explain the graded expression of Kv1.1 toward higher CF, raising a possibility that additional factors may contribute to the differentiation.Thus, we explored the mechanisms of tonotopic differentiation of Kv1.1 in NM, using organotypic culture of chicken brainstem (href="#bib41" rid="bib41" class=" bibr popnode">Sanchez et al., 2011), in which neurons were totally deprived of afferent input. We found that chronic depolarization increased Kv1 current in a level-dependent manner, but the extent was larger at higher-CF regions, causing the tonotopic difference of the current in the culture. The depolarization increased Kv1 current via elevation of [Ca2+]i, whereas it elevated [Ca2+]i similarly irrespective of tonotopic regions. The results showed that the Ca2+-dependent process of Kv1.1 expression was more efficient at higher-CF regions, suggesting the importance of neuronal tonotopic identity as well as pattern of afferent input for the tonotopic differentiation of Kv1.1 in NM.
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