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Different Rho GTPase–dependent signaling pathways initiate sequential steps in the consolidation of long-term potentiation

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

Correspondence to Christopher S. Rex: crex{at}uci.edu

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.

Abbreviations used in this paper: A1R, adenosine A1 receptor; ACSF, artificial cerebral spinal fluid; AMPAR, AMPA receptor; fEPSP, field excitatory postsynaptic potential; FXS, fragile X mental retardation syndrome; ir, immunoreactivity; JPK, jasplakinolide; Lat A, latrunculin A; LTP, long-term potentiation; PAK, p21-activated kinase; PPF, paired pulse facilitation; PSD, postsynaptic density; ROCK, RhoA kinase; str., stratum; TBS, theta burst stimulation.

© 2009 Rex et al.
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