Different Rho GTPase–dependent signaling pathways initiate sequential steps in the consolidation of long-term potentiation |
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Authors: | Christopher S Rex Lulu Y Chen Anupam Sharma Jihua Liu Alex H Babayan Christine M Gall Gary Lynch |
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Institution: | 1.Department of Psychiatry and Human Behavior, 2.Department of Anatomy and Neurobiology, and 3.Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697 |
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Abstract: | The releasable factor adenosine blocks the formation of long-term potentiation (LTP). These experiments used this observation to uncover the synaptic processes that stabilize the potentiation effect. Brief adenosine infusion blocked stimulation-induced actin polymerization within dendritic spines along with LTP itself in control rat hippocampal slices but not in those pretreated with the actin filament stabilizer jasplakinolide. Adenosine also blocked activity-driven phosphorylation of synaptic cofilin but not of synaptic p21-activated kinase (PAK). A search for the upstream origins of these effects showed that adenosine suppressed RhoA activity but only modestly affected Rac and Cdc42. A RhoA kinase (ROCK) inhibitor reproduced adenosine''s effects on cofilin phosphorylation, spine actin polymerization, and LTP, whereas a Rac inhibitor did not. However, inhibitors of Rac or PAK did prolong LTP''s vulnerability to reversal by latrunculin, a toxin which blocks actin filament assembly. Thus, LTP induction initiates two synaptic signaling cascades: one (RhoA-ROCK-cofilin) leads to actin polymerization, whereas the other (Rac-PAK) stabilizes the newly formed filaments. |
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