Tadros M A, Farrell K E, Schofield P R, Brichta A M, Graham B A, Fuglevand A J, Callister R J
School of Biomedical Sciences and Pharmacy, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia;
J Neurophysiol. 2014 Apr;111(7):1487-98. doi: 10.1152/jn.00728.2013. Epub 2014 Jan 8.
Inhibitory synaptic inputs to hypoglossal motoneurons (HMs) are important for modulating excitability in brainstem circuits. Here we ask whether reduced inhibition, as occurs in three murine mutants with distinct naturally occurring mutations in the glycine receptor (GlyR), leads to intrinsic and/or synaptic homeostatic plasticity. Whole cell recordings were obtained from HMs in transverse brainstem slices from wild-type (wt), spasmodic (spd), spastic (spa), and oscillator (ot) mice (C57Bl/6, approximately postnatal day 21). Passive and action potential (AP) properties in spd and ot HMs were similar to wt. In contrast, spa HMs had lower input resistances, more depolarized resting membrane potentials, higher rheobase currents, smaller AP amplitudes, and slower afterhyperpolarization current decay times. The excitability of HMs, assessed by "gain" in injected current/firing-frequency plots, was similar in all strains whereas the incidence of rebound spiking was increased in spd. The difference between recruitment and derecruitment current (i.e., ΔI) for AP discharge during ramp current injection was more negative in spa and ot. GABAA miniature inhibitory postsynaptic current (mIPSC) amplitude was increased in spa and ot but not spd, suggesting diminished glycinergic drive leads to compensatory adjustments in the other major fast inhibitory synaptic transmitter system in these mutants. Overall, our data suggest long-term reduction in glycinergic drive to HMs results in changes in intrinsic and synaptic properties that are consistent with homeostatic plasticity in spa and ot but not in spd. We propose such plasticity is an attempt to stabilize HM output, which succeeds in spa but fails in ot.
舌下运动神经元（HMs）的抑制性突触输入对于调节脑干回路的兴奋性很重要。在这里，我们探讨在三种在甘氨酸受体（GlyR）中具有不同自然发生突变的小鼠突变体中出现的抑制减少是否会导致内在和/或突触稳态可塑性。从野生型（wt）、痉挛型（spd）、痉挛型（spa）和振荡型（ot）小鼠（C57Bl/6，约出生后第21天）的横断脑干切片中的HMs获得全细胞记录。spd和ot HMs的被动和动作电位（AP）特性与wt相似。相比之下，spa HMs具有较低的输入电阻、更去极化的静息膜电位、较高的阈电流、较小的AP幅度以及较慢的超极化后电流衰减时间。通过注入电流/放电频率图中的“增益”评估的HMs兴奋性在所有品系中相似，而spd中反弹放电的发生率增加。在斜坡电流注入期间，AP放电的募集电流和去募集电流之间的差异（即ΔI）在spa和ot中更负。GABAA微小抑制性突触后电流（mIPSC）幅度在spa和ot中增加，但在spd中没有增加，这表明甘氨酸能驱动减弱导致这些突变体中另一个主要的快速抑制性突触传递系统发生代偿性调整。总体而言，我们的数据表明，对HMs的甘氨酸能驱动的长期减少导致内在和突触特性的变化，这与spa和ot中的稳态可塑性一致，但在spd中不一致。我们提出这种可塑性是一种稳定HM输出的尝试，在spa中成功但在ot中失败。
