PKA increases in the olfactory bulb act as unconditioned stimuli and provide evidence for parallel memory systems: Pairing odor with increased PKA creates intermediate- and long-term, but not short-term, memories
- 1Division of BioMedical Sciences and Memorial University of Newfoundland, St. John's, NL, Canada A1B 3V6
- 2Department of Psychology, Memorial University of Newfoundland, St. John's, NL, Canada A1B 3V6
Abstract
Neonatal odor-preference memory in rat pups is a well-defined associative mammalian memory model dependent on cAMP. Previous work from this laboratory demonstrates three phases of neonatal odor-preference memory: short-term (translation-independent), intermediate-term (translation-dependent), and long-term (transcription- and translation-dependent). Here, we use neonatal odor-preference learning to explore the role of olfactory bulb PKA in these three phases of mammalian memory. PKA activity increased normally in learning animals 10 min after a single training trial. Inhibition of PKA by Rp-cAMPs blocked intermediate-term and long-term memory, with no effect on short-term memory. PKA inhibition also prevented learning-associated CREB phosphorylation, a transcription factor implicated in long-term memory. When long-term memory was rescued through increased β-adrenoceptor activation, CREB phosphorylation was restored. Intermediate-term and long-term, but not short-term odor-preference memories were generated by pairing odor with direct PKA activation using intrabulbar Sp-cAMPs, which bypasses β-adrenoceptor activation. Higher levels of Sp-cAMPs enhanced memory by extending normal 24-h retention to 48–72 h. These results suggest that increased bulbar PKA is necessary and sufficient for the induction of intermediate-term and long-term odor-preference memory, and suggest that PKA activation levels also modulate memory duration. However, short-term memory appears to use molecular mechanisms other than the PKA/CREB pathway. These mechanisms, which are also recruited by β-adrenoceptor activation, must operate in parallel with PKA activation.
Footnotes
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↵3 Corresponding author.
E-mail mclean{at}mun.ca.
- Received October 14, 2011.
- Accepted January 30, 2012.
- © 2012 Cold Spring Harbor Laboratory Press
Freely available online through the Learning & Memory Open Access option.