Dissociation between CA3-CA1 synaptic plasticity and associative learning in TgNTRK3 transgenic 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 inNR1andNR2BNMDAreceptor subunits, with

no modification of NR1Ser 896 or NR1Ser 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.