Title : p38 MAP kinase mediates both short-term and long-term synaptic depression in aplysia - Guan_2003_J.Neurosci_23_7317 |
Author(s) : Guan Z , Kim JH , Lomvardas S , Holick K , Xu S , Kandel ER , Schwartz JH |
Ref : Journal of Neuroscience , 23 :7317 , 2003 |
Abstract :
At Aplysia sensory-to-motor neuron synapses, the inhibitory neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFa) produces depression, and serotonin (5-HT) produces facilitation. Short-term depression has been found to result from the activation of a phospholipase A2. The released arachidonate is metabolized by 12-lipoxygenase to active second messengers. We find that FMRFa leads to the phosphorylation and activation of p38 mitogen-activated protein (MAP) kinase. Short-term depression and the release of arachidonate are blocked by the specific p38 kinase inhibitor SB 203580. Both the inhibitor and an affinity-purified antibody raised against recombinant Aplysia p38 kinase injected into sensory neurons prevented long-term depression, which depends on the phosphorylation of translation factors cAMP response element-binding protein 2 (CREB2) and activating transcription factor 2. Facilitation produced by 5-HT, on the other hand, inactivates p38 kinase. Chromatin immunoprecipitation assays indicate that p38 kinase activates CREB2. p38 kinase also is pivotal in the bidirectional regulation of synaptic plasticity: when the kinase is inhibited, brief treatment with 5-HT that normally produces only short-term facilitation now results in long-term facilitation. Conversely, in sensory neurons injected with the activated kinase, long-term facilitation is blocked, and brief exposure to FMRFa, which normally results in short-term depression, results in long-term depression. We conclude that p38 kinase, which itself is bidirectionally regulated by FMRFa and 5-HT, acts as a modulator of synaptic plasticity by positively regulating depression and serving as an inhibitory constraint for facilitation. |
PubMedSearch : Guan_2003_J.Neurosci_23_7317 |
PubMedID: 12917365 |
Guan Z, Kim JH, Lomvardas S, Holick K, Xu S, Kandel ER, Schwartz JH (2003)
p38 MAP kinase mediates both short-term and long-term synaptic depression in aplysia
Journal of Neuroscience
23 :7317
Guan Z, Kim JH, Lomvardas S, Holick K, Xu S, Kandel ER, Schwartz JH (2003)
Journal of Neuroscience
23 :7317