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Publication : Involvement of cholinergic and gabaergic systems in the fragile X knockout mice.

First Author  D'Antuono M Year  2003
Journal  Neuroscience Volume  119
Issue  1 Pages  9-13
PubMed ID  12763063 Mgi Jnum  J:126733
Mgi Id  MGI:3761922 Doi  10.1016/s0306-4522(03)00103-9
Citation  D'Antuono M, et al. (2003) Involvement of cholinergic and gabaergic systems in the fragile X knockout mice. Neuroscience 119(1):9-13
abstractText  Fragile X syndrome is an inherited cause of mental retardation. We used extra- and intracellular recordings in brain slices obtained from wild type and fragile X knockout mice to establish whether bath application of the cholinergic agent carbachol (5 microM) induces different responses in neurons of the subiculum, a limbic structure involved in learning and memory. We found that carbachol diminished excitatory post-synaptic responses induced by CA1 stratum radiatum stimulation in wild type mice, but caused an unexpected increase in knockout animals. Moreover, these responses augmented in knockout mice after carbachol washout, a phenomenon that resembled the muscarinic long-term potentiation seen in wild type mice during application of carbachol and GABA(A) receptor antagonists. We also used paired-pulse stimulation to determine whether the changes in synaptic excitability induced by carbachol were caused by pre- or post-synaptic mechanism. Under control conditions, this protocol induced facilitation in both wild type and knockout mice; in contrast, during carbachol application, this facilitatory effect was seen in wild type mice only.In conclusion, our data highlight for the first time differences in cholinergic and GABA-ergic mechanisms that may contribute to the phenotype of fragile X patients.
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