18. GOALS FOR FELLOWSHIP TRAINING AND CAREER MENTOR Dr. Joel Alexander Dr. Thomas Honpt SUPERVISOR/EMPLOYER Dr. Joel Alexander Dr. Thomas Houpt My goals during this fellowship are to examine the molecular neurobiology underlying learning and memory using conditioned taste aversion (CTA) as a model. More specifically, I would like to examine how molecular changes in the interactions of postsynaptic proteins such as spinophilin and those contained in the post-synaptic density mediate behavioral changes in the whole animal. In this examination, I expect to learn and employ techniques including Western and Northern blotting, antisense technology, immunohistochemistry, polymerase chain reaction (PCR), and in situ hybridization. Mastery of these techniques will allow me to answer many scientific questions throughout my career. By examining CTA, discoveries can be made that may be applied to other forms of associative learning and memory formation. li'][l-'Pii 19. NAME AND DEGREE(S) Dr. Thomas A. Hount 20. POSITION/RANK Associate Professor Biological Science/Program in Neuroscience. 21. RESEARCH INTERESTS/AREAS Neurobiology, Conditioned Taste Aversion, Learning and Memory il_-j =r;l-[ol;I '.-1[e]-.z=}.-f:,. 22. DESCRIPTION (Do not exceed space provided) 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-I 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 bindin_ protein (CREB). PHS 416-1 (Rev. 12/98) Form Page 2 BB cc Individual NRSA Application NAME (Last, first,middle initial) Table of Contents ========================================Section End===========================================
| 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 |
