Effects of neuregulin_1 on long term potentiation in cerebellar granule cells in vitro

Andrew Trembath, The College of Wooster

Abstract

In the brain, controlled variation in synaptic signaling, known as synaptic plasticity, is a complex and highly regulated process believed to give rise to learning and memory. Of particular importance is a major form of synaptic plasticity known as long term potentiation (LTP), disregulation of which has been associated with profound neurological disorders such as schizophrenia. Recent research has focused on the signaling peptide neurgegulin-1 (NRG-1), and its cell surface receptor ErbB4, whose genetic associations with schizophrenia and observed in vitro effects on LTP implicate this signaling system as an important regulator of synaptic plasticity. Here we examined the effects of NRG-1 on a chemically induced model of LTP (cLTP) in cerebellar granule cells (CGCs). First, the previously reported NRG-1 induced depotentiation of cLTP was re-examined through a tritiated binding assay and immunocytochemistry. Next, a novel AM1-43 styryl dye loading assay was developed to investigate the mechanisms of NRG-1 induced cLTP alteration. Finally, CGCs were considered as a model system for future exploration of the regulation of synaptic plasticity. Results presented here suggest that NRG-1 significantly affects AMPA receptor surface expression, and potentially affects synaptic vesicle release. Further, GCGs are proposed as a viable model for studying synaptic plasticity.