Regional differences in hippocampal PKA immunoreactivity after training and reversal training in a spatial Y-maze task

Robbert Havekes*, Marjan Timmer, Eddy A. Van der Zee

*Corresponding author for this work

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Abstract

It is suggested that the hippocampus functions as a comparator by making a comparison between the internal representation and actual sensory information from the environment (for instance, comparing a previously learned location of a food reward with an actual novel location of a food reward in a Y-maze). However, it remains unclear to what extent the various hippocampal regions contribute to this comparator function. One of the proteins known to be crucially involved in the formation of hippocampus-dependent long-term memory is the adenosine 3',5' cyclic monophosphate dependent protein kinase (PKA). Here, we examined region-specific changes in immunoreactivity (ir) of the regulatory II alpha,beta subunits of PKA (PKA RII alpha,beta-ir) in the hippocampus during various stages of spatial learning in a Y-maze reference task. Thereafter, we compared changes in hippocampal PKA RII alpha,beta-ir induced by training and reversal training in which the food reward was relocated to the previously unrewarded arm. We show that: (1) There was a clear correlation between behavioral performance and elevated PKA RII alpha,beta-ir during the acquisition phase of both training and reversal training in area CA3 and dentate gyrus (DG), (2) PKA RII alpha,beta-ir was similarly enhanced in area CA1 during the acquisition phase of reversal training, but did not correlate with behavioral performance, (3) PKA RII alpha beta-ir did not change during training or reversal training in the subiculum (SUB), (4) No changes in PKA RII alpha,beta protein levels were found using Western blotting, and (5) AMPA receptor phosphorylation at serine 845 (S845p; the PKA site on the glutamate receptor 1 subunit (GluR1)), was enhanced selectively during the acquisition phase of reversal training. These findings reveal that training and reversal training induce region-specific changes in hippocampal PKA RII alpha,beta-ir and suggest a differential involvement of hippocampal subregions in match-mismatch detection in case of Y-maze reference learning. Alterations in AMPA receptor regulation at the S845 site seems specifically related to the novelty detector function of the hippocampus important for match-mismatch detection. (C) 2007 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)338-348
Number of pages11
JournalHippocampus
Volume17
Issue number5
DOIs
Publication statusPublished - 2007

Keywords

  • protein kinase A
  • hippocampus
  • learning
  • S845
  • GluR1
  • DEPENDENT PROTEIN-KINASE
  • MUSCARINIC ACETYLCHOLINE-RECEPTORS
  • BIDIRECTIONAL SYNAPTIC PLASTICITY
  • CONTEXTUAL MEMORY CONSOLIDATION
  • LONG-TERM POTENTIATION
  • IMMUNOCYTOCHEMICAL LOCALIZATION
  • NERVOUS-SYSTEM
  • FEAR MEMORY
  • A ACTIVITY
  • RAT-BRAIN

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