Gnegy M E
Department of Pharmacology, University of Michigan, Ann Arbor 48109, USA.
Crit Rev Neurobiol. 2000;14(2):91-129.
Repeated experiences induce a synaptic plasticity in neurons that can be very long lasting. The neurotransmitter, glutamate, acting through N-methyl-D-aspartate (NMDA) receptors is integrally involved in eliciting persistent changes in synaptic function resulting in learning and memory. The permeability of NMDA receptors to Ca2+ implies the close involvement of Ca2+ and the Ca2+-binding protein, calmodulin, in NMDA-induced synaptic plasticity. A notable example of NMDA-induced synaptic plasticity is long-term potentiation in the hippocampal CA1 region. The involvement of Ca2+ and calmodulin in the induction and expression of LTP has been intensively investigated and documented. Less well studied are neurochemical adaptations in another example of NMDA-induced synaptic plasticity, stimulant-induced behavioral sensitization. Although amphetamine and cocaine increase synaptic monoamines, glutamate is involved in the induction and expression of the sensitization. Activating NMDA receptors in dopamine midbrain cell bodies is required for inducing stimulant sensitization, implying a role for Ca2+ in this plasticity. The purpose of this review is to examine the role of Ca2+ and calmodulin in two examples of NMDA-based plasticity, LTP, and stimulant-induced behavioral sensitization. There are similarities in the neuroadaptations, although the role of Ca2+ and calmodulin has not been thoroughly investigated in the stimulant-induced plasticity.
反复的经历会在神经元中诱导出一种持续时间非常长的突触可塑性。神经递质谷氨酸通过N-甲基-D-天冬氨酸（NMDA）受体发挥作用，这一过程与引发突触功能的持续变化从而导致学习和记忆密切相关。NMDA受体对Ca2+的通透性意味着Ca2+和Ca2+结合蛋白钙调蛋白与NMDA诱导的突触可塑性密切相关。NMDA诱导的突触可塑性的一个显著例子是海马CA1区的长时程增强。Ca2+和钙调蛋白在长时程增强的诱导和表达中的作用已得到深入研究和记录。在NMDA诱导的突触可塑性的另一个例子——兴奋剂诱导的行为敏化中，神经化学适应性变化的研究较少。尽管苯丙胺和可卡因会增加突触单胺，但谷氨酸参与了敏化的诱导和表达。在多巴胺中脑细胞体中激活NMDA受体是诱导兴奋剂敏化所必需的，这意味着Ca2+在这种可塑性中发挥作用。本综述的目的是研究Ca2+和钙调蛋白在基于NMDA的两种可塑性——长时程增强和兴奋剂诱导的行为敏化中的作用。尽管Ca2+和钙调蛋白在兴奋剂诱导的可塑性中的作用尚未得到充分研究，但神经适应性变化存在相似之处。
