title: Dissociation between CA3-CA1 synaptic plasticity and associative learning in TgNTRK3 transgenic mice.
abstract: Neurotrophins and their cognate receptors might serve as feedback regulators for the efficacy of synaptic transmission. We analyzed mice overexpressing TrkC (TgNTRK3) for synaptic plasticity and the expression of glutamate receptor subunits. Animals were conditioned using a trace [conditioned stimulus (CS), tone; unconditioned stimulus (US), shock] paradigm. A single electrical pulse presented to the Schaffer collateral-commissural pathway during the CS-US interval evoked a monosynaptic field EPSP (fEPSP) at ipsilateral CA1 pyramidal cells. In wild types, fEPSP slopes increased across conditioning sessions and decreased during extinction, being linearly related to learning evolution. In contrast, fEPSPs in TgNTRK3 animals reached extremely high values, not accompanied with a proportionate increase in their learning curves. Long-term potentiation evoked in conscious TgNTRK3 was also significantly longer lasting than in wild-type mice. These functional alterations were accompanied by significant changes in NR1 and NR2B NMDA receptor subunits, with no modification of NR1(Ser 896) or NR1(Ser 897) phosphorylation. No changes of AMPA and kainate subunits were detected. Results indicate that the NT-3/TrkC cascade could regulate synaptic transmission and plasticity through modulation of glutamatergic transmission at the CA3-CA1 synapse.
authors.affiliation: Genes and Disease Program, Genomic Regulation Center, Universidad Pompeu Fabra, Barcelona Biomedical Research Park, 08003 Barcelona, Spain.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Sahún
authors.forename: José María
authors.initials: JM
authors.lastname: Delgado-García
authors.forename: Alejandro
authors.initials: A
authors.lastname: Amador-Arjona
authors.forename: Albert
authors.initials: A
authors.lastname: Giralt
authors.forename: Jordi
authors.initials: J
authors.lastname: Alberch
authors.forename: Mara
authors.initials: M
authors.lastname: Dierssen
authors.forename: Agnès
authors.initials: A
authors.lastname: Gruart
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D003214:Conditioning, Classical; D005071:Evoked Potentials; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000235:genetics / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000502:physiology*
chemical_list: D009414:Nerve Growth Factors; D016202:N-Methylaspartate; D020812:Receptor, trkC