Conditioned taste aversion (CTA), a form of associative learning, is characterized by behavioral changes after the pairing of a novel palatable taste with a toxin (such as lithium chloride, LiCI), 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. Much of the work done at the cellular level has concentrated on immediate early genes or transcription factors; less is known about the upstream second messenger cascades that may be involved. There is evidence for critical roles for protein kinase activity in CTA; however, the study of termination of this activity by dephosphorylation has not been examined. Therefore, I will focus on protein phosphatase 1 (PP-I), which dephosphorylates substrates and terminates kinase-initiated second messenger activation. Of the serine/threonine phosphatases, PP-1 is the most widely expressed and best characterized, with many substrates including glutamate receptors, protein kinases, transcription factors and structural molecules. By controlling the phosphorylation state of its substrates, PP-1 is involved in the regulation of many cellular functions including neurotransmission, dendritic spine physiology and gene transcription. This proposal will examine the role of PP-1 in CTA learning by using pharmacological antagonists to inhibit PP-1 activity and by determining a time course for the phosphorylation of two PP-1 substrates, the NR1 subunit of the NMDA receptor and cAMP response element binding protein (CREB).
| Oberbeck, Denesa L; McCormack, Stefanie; Houpt, Thomas A (2010) Intra-amygdalar okadaic acid enhances conditioned taste aversion learning and CREB phosphorylation in rats. Brain Res 1348:84-94 |
