Conditioned taste aversion (CTA), a form of associative learning, is characterized by behavioral changes after the pairing of a novel palatable taste such as sucrose with a toxin (such as lithium chloride), resulting in aversive responses to the taste during subsequent presentations. Although much is known about its behavioral characteristics, the molecular mechanisms that underlie CTA learning are not well understood.
This dissertation discusses the investigation of postsynaptic signaling during CTA learning and the role of phosphatase activity has in regulating the cAMP/PKA/CREB/c-Fos signaling cascade as well as subsequent CTA expression. Here, I provide evidence that cAMP is not sufficient to induce either c-Fos, which is necessary for CTA learning, or a CTA when the cAMP analog pCPT-cAMP is paired with a novel taste. Additionally, I show that elevation of cAMP using systemic injections of a phosphodiesterase inhibitor do not enhance CTA learning. I then provide evidence that the gustatory and visceral stimulation that occurs during CTA learning are correlated with alterations in the phosphorylation levels of two PKA substrates: the NR1 subunit of the NMDA receptor and CREB.
The role of phosphatase activity is examined at the neuronal and behavioral levels by administering okadaic acid (OA), a selective inhibitor of the serine/threonine phosphatases PP1/PP2A. Using OA, I provide evidence that PP1/PP2A activity acts as a regulatory constraint during CTA learning by 1) showing increased levels of phosphorylated CREB following OA treatment and CTA acquisition, 2) showing increased levels of c-Fos following co-administration of OA with pCPT-cAMP compared to OA alone or pCPT-cAMP alone, and 3) showing enhanced CTA expression in rats given OA immediately before CTA acquisition.
