A role for hippocampal Rho-ROCK pathway in long-term spatial memory.
Morphological changes, including changes in size, shape, and number of synapses, in neurons have been observed in many species and are thought to be critical for long-term memory storage. Actin filaments are intimately involved in neuronal morphology and regulation of their dynamics can influence memory. Rho GTPase plays a prominent role in this process and has been implicated in both pre- and post-synaptic morphological changes. Therefore, we examined the effect of hippocampal manipulation of Rho and ROCK activity on performance in a spatial memory task. Post-training intrahippocampal infusion of an inhibitor of the downstream effector kinase p160ROCK impaired long-term memory. Furthermore, post-training activation of Rho using lysophosphatidic acid (LPA) enhanced long-term spatial memory. This memory enhancing effect of LPA was not mediated via the Erk cascade, as no change in Erk phosphorylation was observed as a result of its administration. Our results demonstrate a role for the Rho-ROCK pathway in hippocampus-dependent spatial memory.
Dash
Pramod K
PK
Department of Neurobiology and Anatomy, The Vivian L. Smith Center for Neurologic Research, The University of Texas Medical School, Houston, TX, USA. p.dash@uth.tmc.edu
Orsi
Sara A
SA
Moody
Melanie
M
Moore
Anthony N
AN
D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007263:Infusions, Parenteral; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008246:Lysophospholipids; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020928:Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins; C032881:lysophosphatidic acid