Modulation of gene expression following long-term synaptic depression in the striatum.
A number of behavioural and cellular studies have suggested that activity-dependent synaptic plasticity associated with learning and memory may lead to the expression of various genes whose protein products can play a critical 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 long term depression remain to be determined. To elucidate the molecular mechanism underlying activity dependent synaptic remodeling in striatal long term depression, we used the mRNA differential display technology to isolate genes that are induced or modulated by high frequency stimulation of the corticostriatal pathway in a rat brain slice preparation. We have differentially displayed, by means of reverse transcriptase-polymerase chain reaction, mRNA species isolated from striatal slices in which long term depression was induced by tetanic stimuli as well as from slices stimulated at low frequency. We then compared radio-labeled RT-PCR banding patterns to isolate cDNAs that are differentially expressed. Three independent cDNAs were isolated and identified whose mRNA level were enhanced by tetanic stimulation inducing long term depression. We provide evidence that two of these genes encode proteins involved in synaptic vesicle trafficking (dynamin I and amphiphysin II). Moreover, expression of tissue plasminogen activator (t-PA) gene was also increased following striatal long term depression. Our data suggest that a complex pattern of genes acting at presynaptic level and extracellularly may be involved in LTD-associated synaptic remodeling.
Napolitano
M
M
Department of Experimental Medicine and Pathology, University La Sapienza, Viale Regina Elena 324, 00161, Rome, Italy. m.napolitano@capsur.it
Marfia
G A
GA
Vacca
A
A
Centonze
D
D
Bellavia
D
D
Di Marcotullio
L
L
Frati
L
L
Bernardi
G
G
Gulino
A
A
Calabresi
P
P
D000818:Animals; D015152:Blotting, Northern; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D034284:Dynamin I; D034281:Dynamins; D004558:Electric Stimulation; D020558:GTP Phosphohydrolases / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013382:Subtraction Technique
D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C075637:amphiphysin; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins