title: Involvement of the anterior cingulate cortex in the expression of remote spatial memory.
abstract: Although the hippocampus plays a crucial role in the formation of spatial memories, as these memories mature they may become additionally (or even exclusively) dependent on extrahippocampal structures. However, the identity of these extrahippocampal structures that support remote spatial memory is currently not known. Using a Morris water-maze task, we show that the anterior cingulate cortex (ACC) plays a key role in the expression of remote spatial memories in mice. To first evaluate whether the ACC is activated after the recall of spatial memory, we examined the expression of the immediate early gene, c-fos, in the ACC. Fos expression was elevated after expression of a remote (1 month old), but not recent (1 d old), water-maze memory, suggesting that ACC plays an increasingly important role as a function of time. Consistent with the gene expression data, targeted pharmacological inactivation of the ACC with the sodium channel blocker lidocaine blocked expression of remote, but spared recent, spatial memory. In contrast, inactivation of the dorsal hippocampus disrupted expression of spatial memory, regardless of its age. We further showed that inactivation of the ACC blocked expression of remote spatial memory in two different mouse strains, after training with either a hidden or visible platform in a constant location, and using the AMPA receptor antagonist CNQX. Together, our data provide evidence that circuits supporting spatial memory are reorganized in a time-dependent manner, and establish that activity in neurons intrinsic to the ACC is critical for processing remote spatial memories.
authors.affiliation: Program in Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Cátia M
authors.initials: CM
authors.lastname: Teixeira
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Pomedli
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Maei
authors.forename: Nohjin
authors.initials: N
authors.lastname: Kee
authors.forename: Paul W
authors.initials: PW
authors.lastname: Frankland
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D003463:Cues; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008570:Memory, Short-Term / Q000187:drug effects; D011939:Mental Recall / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013028:Space Perception / Q000502:physiology*; D013045:Species Specificity; D013550:Swimming; D013997:Time Factors; D014796:Visual Perception / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D026941:Sodium Channel Blockers; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D008012:Lidocaine