The Effects of Noradrenaline and Action Potential Activity on CPEB3 Expression in Cerebellar Neurons

OBERHELMAN S; BENDER C; LIU SQ

NEW ORLEANS

Jornada; Summer student meeting; 2012

LSUHSC

The regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR2 affects synaptic plasticity by determining if a receptor is Ca2+ permeable. GluR2 mRNA expression has recently been found to increase with stress in mouse cerebellar stellate cells, indicating that the regulation of GluR2 plays a critical role in cerebellar processing of fear-inducing stimuli.  The change from GluR2-lacking to GluR2containing AMPA receptors was found to only occur with enhanced Ca2+ entry.  Cytoplasmic polyadenylation binding element 3 (CPEB3) is a regulator of GluR2 mRNA.  Increase in CPEB3 levels could regulate the rise in GluR2 that occurs with stress. Synaptic plasticity is largely dependent on the activation of varying protein kinases that modify the function of target proteins by means of phosphorylation.  Two kinases that could be involved are protein kinase C (PKC) and protein kinase A (PKA). Though it was recently discovered that GluR2 levels increase in stellate cells with a fear-inducing stimulus, not much is known about the mechanisms that regulate the increase of this AMPA receptor subunit.  Understanding the mechanisms involved in this change in AMPA receptor phenotype and whether a similar process occurs in granule cells is crucial to understanding how the brain processes fear-inducing stimuli in the cerebellum.       We observed that CPEB3 increase occur with noradrenaline treatment in stellate cells and increased action potential activity in granule cells, and that this increase is reduced with the selective PKC and PKA inhibitors Chelerythrine and PKI.