Endogenous neurotrophin-3 regulates short-term plasticity at lateral perforant path-granule cell synapses.
In the adult brain, neurotrophin-3 (NT-3) is mainly localized in dentate granule cells, and its expression is decreased by various stimuli, e.g., seizure activity. We have examined the role of endogenous NT-3 for excitatory synaptic transmission at lateral perforant path-dentate granule cell synapses using hippocampal slices from NT-3 knock-out (+/-) and wild-type (+/+) mice. Paired-pulse facilitation (PPF) and also short-term synaptic plasticity induced by a brief, high-frequency train of afferent stimulation were reduced, but the expression of long-term potentiation was not affected in the NT-3+/- mice. Incubation of the slices with recombinant NT-3 reversed the deficit in PPF through a mechanism requiring de novo protein synthesis, implying that the impaired short-term plasticity does not result from a developmental alteration. No changes of overall presynaptic release probability, measured by the progressive block of NMDA receptor-mediated synaptic currents by MK-801, or desensitization of AMPA receptors were detected. Because NT-3 expression is reduced after focal seizures, impaired short-term facilitation may represent a protective response that limits the propagation of epileptiform activity from the entorhinal cortex to the hippocampus.
Kokaia
M
M
Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, S-221 85 Lund, Sweden.
Asztely
F
F
Olofsdotter
K
K
Sindreu
C B
CB
Kullmann
D M
DM
Lindvall
O
O
D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D009473:Neuronal Plasticity; D020933:Neurotrophin 3; D018408:Patch-Clamp Techniques; D019580:Perforant Pathway / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism; D014176:Protein Biosynthesis; D011760:Pyrrolidinones / Q000494:pharmacology; D018091:Receptors, AMPA / Q000737:chemistry; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry; D011994:Recombinant Proteins / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*
D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D011760:Pyrrolidinones; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; C036466:aniracetam