title: Bidirectional regulation of hippocampal long-term synaptic plasticity and its influence on opposing forms of memory.
abstract: Reference memory characterizes the long-term storage of information acquired through numerous trials. In contrast, working memory represents the short-term acquisition of trial-unique information. A number of studies in the rodent hippocampus have focused on the contribution of long-term synaptic potentiation (LTP) to long-term reference memory. In contrast, little is known about the synaptic plasticity correlates of hippocampal-based components of working memory. Here, we described a mouse with selective expression of a dominant-negative mutant of the regulatory subunit of protein kinase A (PKA) only in two regions of the hippocampus, the dentate gyrus and area CA1. This mouse showed a deficit in several forms of LTP in both hippocampal subregions and a lowered threshold for the consolidation of long-term synaptic depression (LTD). When trained with one trial per day in a water maze task, mutant mice displayed a deficit in consolidation of long-term memory. In contrast, these mice proved to be more flexible after a transfer test and also showed a delay-dependent increased performance in working memory, when repetitive information (proactive interference) was presented. We suggest that through its bidirectional control over synaptic plasticity PKA can regulate opposing forms of memory. The defect in L-LTP disrupts long-term memory consolidation. The persistence of LTD may allow acquisition of new information by restricting the body of previously stored information and suppressing interference.
authors.affiliation: CNRS UMR 5167, Université Claude Bernard, Lyon 69372, France. gaelmalleret@gmail.com
authors.forename: Gaël
authors.initials: G
authors.lastname: Malleret
authors.forename: Juan M
authors.initials: JM
authors.lastname: Alarcon
authors.forename: Guillaume
authors.initials: G
authors.lastname: Martel
authors.forename: Shuichi
authors.initials: S
authors.lastname: Takizawa
authors.forename: Svetlana
authors.initials: S
authors.lastname: Vronskaya
authors.forename: Deqi
authors.initials: D
authors.lastname: Yin
authors.forename: Irene Z
authors.initials: IZ
authors.lastname: Chen
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
authors.forename: Gleb P
authors.initials: GP
authors.lastname: Shumyatsky
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D013997:Time Factors
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases