Stimulation of hippocampal adenylyl cyclase activity dissociates memory consolidation processes for response and place learning.
Procedural and declarative memory systems are postulated to interact in either a synergistic or a competitive manner, and memory consolidation appears to be a highly critical stage for this process. However, the precise cellular mechanisms subserving these interactions remain unknown. To investigate this issue, 24-h retention performances were examined in mice given post-training intrahippocampal injections of forskolin (FK) aiming at stimulating hippocampal adenylyl cyclases (ACs). The injection was given at different time points over a period of 9 h following acquisition in either an appetitive bar-pressing task or water-maze tasks challenging respectively "response memory" and "place memory." Retention testing (24 h) showed that FK injection altered memory formation only when given within a 3- to 6-h time window after acquisition but yielded opposite memory effects as a function of task demands. Retention of the spatial task was impaired, whereas retention of both the cued-response in the water maze and the rewarded bar-press response were improved. Intrahippocampal injections of FK produced an increase in pCREB immunoreactivity, which was strictly limited to the hippocampus and lasted less than 2 h, suggesting that early effects (0-2 h) of FK-induced cAMP/CREB activation can be distinguished from late effects (3-6 h). These results delineate a consolidation period during which specific cAMP levels in the hippocampus play a crucial role in enhancing memory processes mediated by other brain regions (e.g., dorsal or ventral striatum) while eliminating interference by the formation of hippocampus-dependent memory.
Martel
Guillaume
G
Laboratoire de Neurosciences Cognitives, Université Bordeaux I, Centre Nationale de la Recherche Scientifique Unite Mixte de Recherche (CNRS UMR) 5106, 33405 Talence cedex, France.
Millard
Annabelle
A
Jaffard
Robert
R
Guillou
Jean-Louis
JL
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000008:administration & dosage; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D020536:Enzyme Activators / Q000008:administration & dosage; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D010766:Phosphorylation; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D017362:Cyclic AMP Response Element-Binding Protein; D020536:Enzyme Activators; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases