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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-5-22
pubmed:abstractText
Induction of long-term depression (LTD) in rat striatal slices revealed that this form of synaptic plasticity is coupled to an increased expression of tissue-plasminogen activator (t-PA) mRNA, as detected by the mRNA differential display technique. To further investigate the involvement of this gene in synaptic remodelling following striatal LTD, we recorded electrical activity from mice lacking the gene encoding t-PA (t-PA-KO) and from wild-type (WT) mice. Tetanic stimulation induced LTD in the large majority of striatal neurons recorded from WT mice. Conversely, LTD was absent in a significant proportion of striatal neurons obtained from mice lacking t-PA. Electrophysiological recordings obtained from hippocampal slices in the CA1 area showed that mainly the late phase of long-term potentiation (LTP) was reduced in t-PA-KO mice. Learning and memory-related behavioural abnormalities were also found in these transgenic mice. Disruption of the t-PA gene, in fact, altered both the context conditioning test, a hippocampus-related behavioural task, and the two-way active avoidance, a striatum-dependent task. In an open field object exploration task, t-PA-KO mice expressed deficits in habituation and reactivity to spatial change that are consistent with an altered hippocampal function. Nevertheless, decreased rearing and poor initial object exploration were also observed, further suggesting an altered striatal function. These data indicate that t-PA plays a critical role in the formation of various forms of synaptic plasticity and memory.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1002-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10762331-Animals, pubmed-meshheading:10762331-Blotting, Northern, pubmed-meshheading:10762331-Electric Stimulation, pubmed-meshheading:10762331-Electrophysiology, pubmed-meshheading:10762331-Fear, pubmed-meshheading:10762331-Gene Expression Regulation, pubmed-meshheading:10762331-Habituation, Psychophysiologic, pubmed-meshheading:10762331-Long-Term Potentiation, pubmed-meshheading:10762331-Male, pubmed-meshheading:10762331-Memory, pubmed-meshheading:10762331-Mice, pubmed-meshheading:10762331-Mice, Knockout, pubmed-meshheading:10762331-Motor Activity, pubmed-meshheading:10762331-Neostriatum, pubmed-meshheading:10762331-Neuronal Plasticity, pubmed-meshheading:10762331-RNA, Messenger, pubmed-meshheading:10762331-Rats, pubmed-meshheading:10762331-Rats, Wistar, pubmed-meshheading:10762331-Space Perception, pubmed-meshheading:10762331-Synapses, pubmed-meshheading:10762331-Tissue Plasminogen Activator
pubmed:year
2000
pubmed:articleTitle
Tissue plasminogen activator controls multiple forms of synaptic plasticity and memory.
pubmed:affiliation
Clinica Neurologica, Dip. Neuroscienze, Università di Tor Vergata, Via di Tor Vergata 135, Rome 00133, Italy. calabre@uniroma2.it
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't