Intermediate- and long-term recognition memory deficits in Tg2576 mice are reversed with acute calcineurin inhibition

Giulio Taglialatela, Dale Hogan, Wen Ru Zhang, Kelly T. Dineley

Research output: Contribution to journalArticle

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Abstract

The Tg2576 transgenic mouse is an extensively characterized animal model for Alzheimer's disease (AD). Similar to AD, these mice suffer from progressive decline in several forms of declarative memory including contextual fear conditioning and novel object recognition (NOR). Recent work on this and other AD animal models suggests that initial cognitive deficits are due to synaptic dysfunction that, with the correct intervention, are fully treatable. We recently reported that acute calcineurin (CaN) inhibition with FK506 ameliorates one form of declarative memory (contextual fear conditioning) impairment in 5 months old Tg2576. This study tested whether acute CaN inhibition rescues deficits in an additional form of declarative memory, spontaneous object recognition, by employing the NOR paradigm. Furthermore, we determined whether FK506 rescue of NOR deficits depends on the retention interval employed and therefore is restricted to short-term, intermediate-term, or long-term memory (STM, ITM or LTM, respectively). In object recognition, Tg2576 are unimpaired when NOR is tested as a STM task and CaN inhibition with FK506 does not influence NOR STM performance in Tg2576 or WT mice. Tg2576 were impaired in NOR compared to WT mice when a 4 or 24 h retention interval was employed to model ITM and LTM, respectively. Acute CaN inhibition prior to and during the training session reversed these deficits in Tg2576 mice with no effect on WT performance. Our findings demonstrate that aberrant CaN activity mediates object recognition deficits in 5 months old Tg2576 when NOR is employed as a test for ITM and LTM. In human AD, CaN inhibition may lead the way for therapeutics to improve declarative memory performance as demonstrated in a mouse model for AD.

Original languageEnglish (US)
Pages (from-to)95-99
Number of pages5
JournalBehavioural Brain Research
Volume200
Issue number1
DOIs
StatePublished - Jun 8 2009

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Keywords

  • Alzheimer's disease
  • FK506
  • Intermediate-term memory
  • Long-term memory
  • Novel object recognition
  • Retention interval
  • Short-term memory

ASJC Scopus subject areas

  • Behavioral Neuroscience

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