P38 MAP KINASE MEDIATES BOTH SHORT-TERM AND LONG-TERM SYNAPTIC DEPRESSION IN APLYSIA
SCIE
SCOPUS
- Title
- P38 MAP KINASE MEDIATES BOTH SHORT-TERM AND LONG-TERM SYNAPTIC DEPRESSION IN APLYSIA
- Authors
- Guan, ZH; Kim, JH; Lomvardas, S; Holick, K; Xu, SQ; K; el, ER; Schwartz, JH
- Date Issued
- 2003-08-13
- Publisher
- SOC NEUROSCIENCE
- 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 A(2). 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.
- Keywords
- Aplysia; histone deacetylase; long-term depression; long-term facilitation; phospholipase A(2); p38 MAP kinase; ACTIVATED PROTEIN-KINASE; CYTOSOLIC PHOSPHOLIPASE A(2); SENSORY NEURONS; ARACHIDONIC-ACID; MOLECULAR-BIOLOGY; CAM KINASE; FACILITATION; PLASTICITY; STRESS; MEMORY
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/28385
- ISSN
- 0270-6474
- Article Type
- Article
- Citation
- JOURNAL OF NEUROSCIENCE, vol. 23, no. 19, page. 7317 - 7325, 2003-08-13
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.