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The Journal of Neuroscience, November 1, 1998, 18(21):8730-8739
Endogenous Neurotrophin-3 Regulates Short-Term Plasticity at
Lateral Perforant Path-Granule Cell Synapses
Merab
Kokaia1,
Fredrik
Asztely1,
Klara
Olofsdotter1,
Carlos Balet
Sindreu1,
Dimitri M.
Kullmann2, and
Olle
Lindvall1
1 Section of Restorative Neurology, Wallenberg
Neuroscience Center, University Hospital, S-221 85 Lund, Sweden, and
2 Department of Clinical Neurology, Institute of Neurology,
Queen Square, London WC1N 3BG, United Kingdom
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.
Key words:
neurotrophin-3; synaptic plasticity; dentate gyrus; hippocampal slices; whole-cell patch-clamp; knock-out mice
Copyright © 1998 Society for Neuroscience 0270-6474/98/18218730-10$05.00/0
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