Ishikawa Masago, Mu Ping, Moyer Jason T, Wolf John A, Quock Raymond M, Davies Neal M, Hu Xiu-Ti, Schlüter Oliver M, Dong Yan
Program in Neuroscience, Washington State University, Pullman, Washington 99164-6520, USA.
J Neurosci. 2009 May 6;29(18):5820-31. doi: 10.1523/JNEUROSCI.5703-08.2009.
Stable brain function relies on homeostatic maintenance of the functional output of individual neurons. In general, neurons function by converting synaptic input to output as action potential firing. To determine homeostatic mechanisms that balance this input-output/synapse-membrane interaction, we focused on nucleus accumbens (NAc) neurons and demonstrated a novel form of synapse-to-membrane homeostatic regulation, homeostatic synapse-driven membrane plasticity (hSMP). Through hSMP, NAc neurons adjusted their membrane excitability to functionally compensate for basal shifts in excitatory synaptic input. Furthermore, hSMP was triggered by synaptic NMDA receptors (NMDARs) and expressed by the modification of SK-type Ca(2+)-activated potassium channels. Moreover, hSMP in NAc neurons was abolished in rats during a short- (2 d) or long- (21 d) term withdrawal from repeated intraperitoneal injections of cocaine (15 mg/kg/d, 5 d). These results suggest that hSMP is a novel form of synapse-to-membrane homeostatic plasticity and dysregulation of hSMP may contribute to cocaine-induced cellular alterations in the NAc.
稳定的脑功能依赖于单个神经元功能输出的稳态维持。一般来说，神经元通过将突触输入转换为动作电位发放的输出而起作用。为了确定平衡这种输入 - 输出/突触 - 膜相互作用的稳态机制，我们聚焦于伏隔核（NAc）神经元，并证明了一种新型的从突触到膜的稳态调节形式，即稳态突触驱动的膜可塑性（hSMP）。通过hSMP，NAc神经元调节其膜兴奋性，以在功能上补偿兴奋性突触输入的基础变化。此外，hSMP由突触N - 甲基 - D - 天冬氨酸受体（NMDARs）触发，并通过SK型钙激活钾通道的修饰来表达。此外，在大鼠从重复腹腔注射可卡因（15mg/kg/d，5天）短期（2天）或长期（21天）撤药期间，NAc神经元中的hSMP被消除。这些结果表明，hSMP是一种新型的从突触到膜的稳态可塑性，hSMP的失调可能导致可卡因诱导的NAc细胞改变。
