Journal article
Genetic and pharmacological demonstration of a role for cyclic AMP-dependent protein kinase-mediated suppression of protein phosphatases in gating the expression of late LTP
The European journal of neuroscience, Vol.16(10), pp.1871-1876
11/2002
DOI: 10.1046/j.1460-9568.2002.02260.x
PMID: 12453050
Abstract
Protein kinases and phosphatases play antagonistic roles in regulating hippocampal long-term potentiation (LTP), with kinase inhibition and phosphatase activation both impairing LTP. The late phase of LTP (L-LTP) requires activation of cAMP-dependent protein kinase (PKA) for its full expression. One way in which PKA may critically modulate L-LTP is by relieving an inhibitory constraint imposed by protein phosphatases. Using mutant PKA mice [R(AB) transgenic mice] that have genetically reduced hippocampal PKA activity, we show that deficient L-LTP in area CA1 of mutant hippocampal slices is rescued by acute application of two inhibitors of protein phosphatase-1 and protein phosphatase-2A (PP1/2A) (okadaic acid and calyculin A). Furthermore, synaptic facilitation induced by forskolin, an adenylyl cyclase activator, was impaired in R(AB) transgenics and was also rescued by a PP1/2A inhibitor in mutant slices. Inhibition of PP1/2A did not affect early LTP (E-LTP) or basal synaptic transmission in mutant and wildtype slices. Our data show that genetic inhibition of PKA impairs L-LTP by reducing PKA-mediated suppression of PP1/2A.
Details
- Title: Subtitle
- Genetic and pharmacological demonstration of a role for cyclic AMP-dependent protein kinase-mediated suppression of protein phosphatases in gating the expression of late LTP
- Creators
- Newton H Woo - Department of Physiology, University of Alberta School of Medicine, Edmonton, Alberta, T6G 2H7, CanadaTed AbelPeter V Nguyen
- Resource Type
- Journal article
- Publication Details
- The European journal of neuroscience, Vol.16(10), pp.1871-1876
- Publisher
- France
- DOI
- 10.1046/j.1460-9568.2002.02260.x
- PMID
- 12453050
- ISSN
- 0953-816X
- eISSN
- 1460-9568
- Grant note
- HD26979 / NICHD NIH HHS AG18199 / NIA NIH HHS MH60244 / NIMH NIH HHS
- Language
- English
- Date published
- 11/2002
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065833502771
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