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.Weanalyzed mice</p><p>overexpressing TrkC (TgNTRK3) for synaptic plasticity and the expression of glutamate receptor subunits. Animals were conditioned</p><p>using a trace [conditioned stimulus (CS), tone; unconditioned stimulus (US), shock] paradigm. A single electrical pulse presented to the</p><p>Schaffer collateral– commissural pathway during the CS–US interval evoked a monosynaptic field EPSP (fEPSP) at ipsilateral CA1</p><p>pyramidal cells. In wild types, fEPSP slopes increased across conditioning sessions and decreased during extinction, being linearly</p><p>related to learning evolution. In contrast, fEPSPs in TgNTRK3 animals reached extremely high values, not accompanied with a proportionate</p><p>increase in their learning curves. Long-term potentiation evoked in conscious TgNTRK3 was also significantly longer lasting than</p><p>in wild-type mice. These functional alterations were accompanied by significant changes inNR1andNR2BNMDAreceptor subunits, with</p><p>no modification of NR1Ser 896 or NR1Ser 897 phosphorylation. No changes of AMPA and kainate subunits were detected. Results indicate</p><p>that the NT-3/TrkC cascade could regulate synaptic transmission and plasticity through modulation of glutamatergic transmission at the</p><p>CA3–CA1 synapse.