On the participation of hippocampal PKC in acquisition, consolidation and reconsolidation of spatial memory

• Published in: Neuroscience Vol. 147; no. 1; pp. 37 - 45
• Main Authors: Bonini, J.S, Da Silva, W.C, Bevilaqua, L.R.M, Medina, J.H, Izquierdo, I, Cammarota, M
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.06.2007; Elsevier
• Subjects: Animals; Avoidance Learning - drug effects; Avoidance Learning - physiology; Biological and medical sciences; Carbazoles - administration & dosage; consolidation; Drug Administration Schedule; Enzyme Inhibitors - administration & dosage; Fundamental and applied biological sciences. Psychology; hippocampus; Hippocampus - drug effects; Hippocampus - enzymology; Indoles - administration & dosage; learning; Male; Maze Learning - drug effects; Maze Learning - physiology; memory; Mental Recall - drug effects; Mental Recall - physiology; Microinjections; Neurology; PKC; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Rats; Rats, Wistar; reconsolidation; Space Perception - drug effects; Space Perception - physiology; Vertebrates: nervous system and sense organs; novel PKC; MWM; memory; Morris water maze; hippocampus; LTM; inhibitory avoidance; PKC; nPKC; learning; aPKC; cPKC; DAG; 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrollo[3,4-c]carbazole; consolidation; reconsolidation; conventional PKC; long-term memory; atypical PKC; IA; Gö6976; diacylglycerol; Learning; Acquisition process; Central nervous system; Hippocampus; Encephalon; Spatial memory
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2007.04.013

Abstract Memory consolidation involves a sequence of temporally defined and highly regulated changes in the activation state of several signaling pathways that leads to the lasting storage of an initially labile trace. Despite appearances, consolidation does not make memories permanent. It is now known that upon retrieval well-consolidated memories can become again vulnerable to the action of amnesic agents and in order to persist must undergo a protein synthesis–dependent process named reconsolidation. Experiments with genetically modified animals suggest that some PKC isoforms are important for spatial memory and earlier studies indicate that several PKC substrates are activated following spatial learning. Nevertheless, none of the reports published so far analyzed pharmacologically the role played by PKC during spatial memory processing. Using the conventional PKC and PKCμ inhibitor 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2,3-a]pyrrollo[3,4-c]carbazole (Gö6976) we found that the activity of these kinases is required in the CA1 region of the rat dorsal hippocampus for acquisition and consolidation of spatial memory in the Morris water maze learning task. Our results also show that when infused into dorsal CA1 after non-reinforced retrieval, Gö6976 produces a long-lasting amnesia that is independent of the strength of the memory trace, suggesting that post-retrieval activation of hippocampal PKC is essential for persistence of spatial memory.