Signal transduction is basic to understanding synaptic plasticity, particularly changes in a neuron's activities resulting from stimulation or training. These changes are thought to underlie normal behavioral modifications, such a learning and memory. In addition, alterations in these molecular processes, produced by genetic abnormalities, unfavorable environment, or as a result of disease or substance abuse, are fundamental to the pathophysiology of mental disorders. Identified sensory neurons mediate defensive reflexes that can be sensitized in the marine mollusk, Aplysia. We plan to continue studying how the two isoforms of protein kinase C (PKC) that are present in aplysia neurons synapses. LTF underlies behavioral sensitization, which is a simple form of learning and memory. As in the consolidation of vertebrate learning, LTF requires the synthesis of new proteins. Activation of transcription factors is necessary to promote a molecular cascade in which effector enzymes and new structural proteins needed for the maintenance and consolidation of memory storage are synthesized. One of the transcription factors shown to be necessary for producing LTF is ApC/EBP. During the past grant period, we found that protein phosphorylation by PKC is required for activating ApC/EBP, an early response gene in the sensory neurons. PKC phosphorylation is needed also for turnover of the transcription activator protein by degradation through the ATP-ubiquitin-proteasome pathway. We now aim to characterize the mechanisms by which PKC phosphorylation regulates the ongoing cascade of new protein synthesis that is the molecular basis of memory storage in LTF.
| Hernández, A Iván; Wolk, Jason; Hu, Jiang-Yuan et al. (2009) Poly-(ADP-ribose) polymerase-1 is necessary for long-term facilitation in Aplysia. J Neurosci 29:9553-62 |
| Kurosu, Takeshi; Hernandez, A Ivan; Schwartz, James H (2007) Serotonin induces selective cleavage of the PKA RI subunit but not RII subunit in Aplysia neurons. Biochem Biophys Res Commun 359:563-7 |
