Bidirectional regulation of hippocampal long-term synaptic plasticity and its influence on opposing forms of memory

Gaël Malleret, Juan M. Alarcon, Guillaume Martel, Shuichi Takizawa, Svetlana Vronskaya, Deqi Yin, Irene Z. Chen, Eric R. Kandel, Gleb P. Shumyatsky

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


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 kinaseA(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.

Original languageEnglish (US)
Pages (from-to)3813-3825
Number of pages13
JournalJournal of Neuroscience
Issue number10
StatePublished - Mar 10 2010

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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