On the participation of hippocampal PKC in acquisition, consolidation and reconsolidation of spatial memory.
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 PKCmu 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.
Bonini
J S
JS
Centro de Memória, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6690, Porto Alegre, RS 90610-000, Brazil.
Da Silva
W C
WC
Bevilaqua
L R M
LR
Medina
J H
JH
Izquierdo
I
I
Cammarota
M
M
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D002227:Carbazoles / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*
D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; C081021:Go 6976; D011493:Protein Kinase C