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J Neurosci ; 18(21): 8730-9, 1998 Nov 01.
Article in English | MEDLINE | ID: mdl-9786980

ABSTRACT

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.


Subject(s)
Dentate Gyrus/physiology , Nerve Growth Factors/physiology , Perforant Pathway/physiology , Synapses/physiology , Animals , Dentate Gyrus/drug effects , Excitatory Postsynaptic Potentials , In Vitro Techniques , Long-Term Potentiation , Membrane Potentials/drug effects , Mice , Mice, Knockout , Mossy Fibers, Hippocampal/physiology , Nerve Growth Factors/genetics , Nerve Growth Factors/pharmacology , Neuronal Plasticity , Neurotrophin 3 , Patch-Clamp Techniques , Perforant Pathway/drug effects , Presynaptic Terminals/metabolism , Protein Biosynthesis , Pyrrolidinones/pharmacology , Receptors, AMPA/chemistry , Receptors, N-Methyl-D-Aspartate/chemistry , Recombinant Proteins/pharmacology
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