Modulation of gene expression following long-term synaptic depression in the striatum

A number of behavioural and cellular studies have suggested that activity-d ependent synaptic plasticity associated with learning and memory may lead t o the expression of various genes whose protein products can play a critica l role in memory acquisition and consolidation. Long-term potentiation (LTP ) and long-term depression (LTD) represent two forms of synaptic plasticity which have been widely studied by electrophysiological techniques. However , the molecular mechanisms at target gene involved in the generation of lon g term depression remain to be determined. To elucidate the molecular mecha nism underlying activity dependent synaptic remodeling in striatal long ter m depression, we used the mRNA differential display technology to isolate g enes that are induced or modulated by high frequency stimulation of the cor ticostriatal pathway in a rat brain slice preparation. We have differential ly displayed, by means of reverse transcriptase-polymerase chain reaction, mRNA species isolated from striatal slices in which long term depression wa s induced by tetanic stimuli as well as from slices stimulated at low frequ ency. We then compared radio-labeled RT-PCR banding patterns to isolate cDN As that are differentially expressed. Three independent cDNAs were isolated and identified whose mRNA level were enhanced by tetanic stimulation induc ing long term depression. We provide evidence that two of these genes encod e proteins involved in synaptic vesicle trafficking (dynamin I and amphiphy sin ZI), Moreover, expression of tissue plasminogen activator (t-PA) gene w as also increased following striatal long term depression. Our data suggest that a complex pattern of genes acting at presynaptic level and extracellu larly may be involved in LTD-associated synaptic remodeling. (C) 1999 Publi shed by Elsevier Science B.V. All rights reserved.