| Abstract No.: | A-B1025 |
| Country: | Canada |
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| Title: | CROSS-INHIBITION BETWEEN THE PKA AND THE PKC SIGNALLING PATHWAYS IN SYNAPTIC PLASTICITY |
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| Authors/Affiliations: | 1 Carole Abi Farah; 1 Xiaotang Fan; 1 Wayne Sossin;
1 Montreal Neurological Institute, QC, Canada
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| Content: | Protein kinase Cs are important mediators of synaptic plasticity. In Aplysia, synaptic facilitation is mediated by the neurotransmitter serotonin (5HT). Interestingly, there is a distinction between PKA and PKC in persistent increases in synaptic strength [intermediate-term facilitation (ITF)] caused by 5HT. ITF induced by spaced application of 5HT depends on persistent activation of PKA but not PKC whereas continuous or “massed” application of 5HT leads to ITF and persistently activates PKC, but does not persistently activate PKA. We have previously shown that the novel PKC Apl II is the major isoform to be translocated in response to 5HT in sensory neurons and that this requires both phospholipase C and phospholipase D activation. While doing these experiments, we noticed that translocation of PKC Apl II was sensitive to the pattern of stimulation. Spaced applications of 5HT strongly desensitize PKC Apl II translocation, while prolonged applications of 5HT only weakly desensitize PKC. Furthermore, blocking PKC activation using phospholipase C inhibitor does not affect desensitization by spaced applications of 5HT, suggesting hetero-desensitization through another pathway. We hypothesize that activation of PKA desensitizes the response to PKC. Coupled with previous observations that PKC can down-regulate activation of PKA, we propose that a ‘battle’ between the kinases occurs and the winner is determined by the pattern of stimulation. In the present study, we show that inhibition of PKA completely blocks desensitization of PKC Apl II translocation in response to spaced applications of 5HT. Furthermore, we show that adding the PKA inhibitor only after 5HT is washed off also blocks PKC Apl II desensitization. In contrast, PKC Apl II desensitization during massed training is only weakly affected by the PKA inhibitor. We also parametrize the PKC Apl II response to 5HT and show that there is no desensitization 5 min after the first 5HT pulse. Desensitization is maximal 30 min after the first 5HT pulse and complete recovery is observed 60 min after the first pulse. We are currently testing whether desensitization is affected by translation inhibitors. This work will provide a biochemical understanding of the difference between spaced and massed training, elucidating a fundamental aspect of learning and memory. |
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