Ca2+/calmodulin signaling in NMDA-induced synaptic plasticity.
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.
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Department of Pharmacology, University of Michigan, Ann Arbor 48109, USA.
D000818:Animals; D001921:Brain / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D002147:Calmodulin; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D002118:Calcium