title: Intrahippocampal Anisomycin Impairs Spatial Performance on the Morris Water Maze.
abstract: New memories are thought to be solidified (consolidated) by de novo synthesis of proteins in the period subsequent to learning. This view stems from the observation that protein synthesis inhibitors, such as anisomycin (ANI), administered during this consolidation period cause memory impairments. However, in addition to blocking protein synthesis, intrahippocampal infusions of ANI cause the suppression of evoked and spontaneous neural activity, suggesting that ANI could impair memory expression by simply preventing activity-dependent brain functions. Here, we evaluated the influence of intrahippocampal ANI infusions on allocentric spatial navigation using the Morris water maze, a task well known to require dorsal hippocampal integrity. Young, adult male Sprague Dawley rats were implanted with bilateral dorsal hippocampal cannulae, and their ability to learn the location of a hidden platform was assessed before and following infusions of ANI, TTX, or vehicle (PBS). Before infusion, all groups demonstrated normal spatial navigation (training on days 1 and 2), whereas 30 min following infusions (day 3) both the ANI and TTX groups showed significant impairments in allocentric navigation, but not visually cued navigation, when compared with PBS-treated animals. Spatial navigational deficits appeared to resolve on day 4 in the ANI and TTX groups, 24 h following infusion. These results show that ANI and TTX inhibit the on-line function of the dorsal hippocampus in a similar fashion and highlight the importance of neural activity as an intervening factor between molecular and behavioral processes.
  
  
  CONCLUSIONS
  The permanence of memories has long thought to be mediated by the production of new proteins, because protein synthesis inhibitors can block retrieval of recently learned information. However, protein synthesis inhibitors may have additional detrimental effects on neurobiological function. Here we show that anisomycin, a commonly used protein synthesis inhibitor in memory research, impairs on-line brain function in a way similar to an agent that eliminates electrical neural activity. Since disruption of neural activity can also lead to memory loss, it may be that memory permanence is mediated by neural rehearsal following learning.
authors.affiliation: Department of Psychology, University of Alberta, Edmonton, Alberta, Canada T6G 2E9.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Dubue
authors.affiliation: Department of Psychology, University of Alberta, Edmonton, Alberta, Canada T6G 2E9.
authors.forename: Ty L
authors.initials: TL
authors.lastname: McKinney
authors.affiliation: Department of Psychology, University of Alberta, Edmonton, Alberta, Canada T6G 2E9, Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2E1.
authors.forename: Dallas
authors.initials: D
authors.lastname: Treit
authors.affiliation: Department of Psychology, University of Alberta, Edmonton, Alberta, Canada T6G 2E9, Department of Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7, and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada T6G 2E1 clayton.dickson@ualberta.ca.
authors.forename: Clayton T
authors.initials: CT
authors.lastname: Dickson
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013037:Spatial Behavior / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D011500:Protein Synthesis Inhibitors; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D000841:Anisomycin
keywords: anisomycin; behavioral neuroscience; hippocampus; neural activity; protein synthesis inhibitor