Amarillo Yimy, Tissone Angela I, Mato Germán, Nadal Marcela S
Departamento de Física Médica, Centro Atómico Bariloche and Instituto Balseiro, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), San Carlos de Bariloche, Río Negro, Argentina.
Gerencia de Área Investigación y Aplicaciones no Nucleares, Gerencia de Física, Departamento Sistemas Complejos y Altas Energías, División Física Estadística e Interdisciplinaria, Centro Atómico Bariloche, San Carlos de Bariloche, Río Negro, Argentina.
J Neurophysiol. 2018 Jun 1;119(6):2358-2372. doi: 10.1152/jn.00867.2017. Epub 2018 Mar 21.
Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (<4 Hz), which are the physiological oscillations during non-rapid eye movement sleep or pathological oscillations during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that upregulation of the small and neglected inward rectifier potassium current I induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mouse TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explains how the unique properties of I enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage- and time-dependent interaction of I and hyperpolarization-activated cationic current I that endows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. Bifurcation analysis of conductance-based models of increasing complexity demonstrates that I induces bistability of the membrane potential at the same time that it induces sustained oscillations in combination with I and increases the robustness of low threshold-activated calcium current I-mediated oscillations. NEW & NOTEWORTHY The strong inwardly rectifying potassium current I of thalamocortical neurons displays a region of negative slope conductance in the current-voltage relationship that generates potassium currents activated by hyperpolarization. Bifurcation analysis shows that I induces bistability of the membrane potential; generates sustained subthreshold oscillations by interacting with the hyperpolarization-activated cationic current I; and increases the robustness of oscillations mediated by the low threshold-activated calcium current I. Upregulation of I in thalamocortical neurons induces repetitive burst firing at slow and delta frequency bands (<4 Hz).
超极化丘脑皮质（TC）神经元的缓慢重复爆发式放电与整体慢节律（<4Hz）相关，慢节律是非快速眼动睡眠期间的生理振荡或特发性癫痫期间的病理振荡。TC神经元的起搏器活动取决于几种阈下电导的表达，这些电导以行为依赖的方式受到调节。在这里，我们表明小的且常被忽视的内向整流钾电流I的上调会在慢波和δ频段诱导重复爆发式放电。我们通过动态钳制操纵Kir最大电导，在脑片的小鼠TC神经元中证明了这一点。我们还进行了全面的理论分析，解释了电流I的独特特性如何使其能够在TC神经元中诱导缓慢的周期性爆发。我们描述了一种基于电流I和超极化激活阳离子电流I的电压和时间依赖性相互作用的新离子机制，该机制赋予TC神经元在非常低的频率（甚至低于0.5Hz）自发振荡的能力。对复杂度不断增加的基于电导的模型进行分岔分析表明，电流I在诱导膜电位双稳性的同时，与电流I共同诱导持续振荡，并增强低阈值激活钙电流I介导的振荡的稳健性。新发现与值得注意的是，丘脑皮质神经元强大的内向整流钾电流I在电流-电压关系中显示出负斜率电导区域，该区域产生由超极化激活的钾电流。分岔分析表明，电流I诱导膜电位双稳性；通过与超极化激活阳离子电流I相互作用产生持续的阈下振荡；并增强由低阈值激活钙电流I介导的振荡的稳健性。丘脑皮质神经元中电流I的上调会在慢波和δ频段（<4Hz）诱导重复爆发式放电。
