Zeberg Hugo, Robinson Hugh P C, Århem Peter
Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; and Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom
Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
J Neurophysiol. 2015 Jan 15;113(2):537-49. doi: 10.1152/jn.00907.2013. Epub 2014 Oct 22.
Several types of intrinsic dynamics have been identified in brain neurons. Type 1 excitability is characterized by a continuous frequency-stimulus relationship and, thus, an arbitrarily low frequency at threshold current. Conversely, Type 2 excitability is characterized by a discontinuous frequency-stimulus relationship and a nonzero threshold frequency. In previous theoretical work we showed that the density of Kv channels is a bifurcation parameter, such that increasing the Kv channel density in a neuron model transforms Type 1 excitability into Type 2 excitability. Here we test this finding experimentally, using the dynamic clamp technique on Type 1 pyramidal cells in rat cortex. We found that increasing the density of slow Kv channels leads to a shift from Type 1 to Type 2 threshold dynamics, i.e., a distinct onset frequency, subthreshold oscillations, and reduced latency to first spike. In addition, the action potential was resculptured, with a narrower spike width and more pronounced afterhyperpolarization. All changes could be captured with a two-dimensional model. It may seem paradoxical that an increase in slow K channel density can lead to a higher threshold firing frequency; however, this can be explained in terms of bifurcation theory. In contrast to previous work, we argue that an increased outward current leads to a change in dynamics in these neurons without a rectification of the current-voltage curve. These results demonstrate that the behavior of neurons is determined by the global interactions of their dynamical elements and not necessarily simply by individual types of ion channels.
在脑神经元中已发现几种类型的内在动力学。1型兴奋性的特征是频率 - 刺激关系连续，因此在阈值电流下频率可任意低。相反，2型兴奋性的特征是频率 - 刺激关系不连续且阈值频率非零。在先前的理论工作中，我们表明钾离子通道（Kv）的密度是一个分岔参数，在神经元模型中增加Kv通道密度会将1型兴奋性转变为2型兴奋性。在此，我们使用动态钳技术对大鼠皮层的1型锥体细胞进行实验验证这一发现。我们发现增加慢Kv通道的密度会导致从1型阈值动力学转变为2型阈值动力学，即出现明显的起始频率、阈下振荡以及首次放电潜伏期缩短。此外，动作电位也发生了重塑，峰宽变窄且超极化后电位更明显。所有这些变化都可以用二维模型来捕捉。慢K通道密度增加会导致更高的阈值放电频率，这似乎有些矛盾；然而，这可以用分岔理论来解释。与先前的工作不同，我们认为外向电流增加会导致这些神经元的动力学发生变化，而电流 - 电压曲线并未发生整流。这些结果表明，神经元的行为是由其动态元件的全局相互作用决定的，而不一定仅仅由个别类型的离子通道决定。
