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The Journal of Neuroscience, July 1, 1999, 19(13):5619-5631
Actions of Brain-Derived Neurotrophic Factor in Slices from Rats
with Spontaneous Seizures and Mossy Fiber Sprouting in the Dentate
Gyrus
Helen E.
Scharfman1, 2,
Jeffrey H.
Goodman1, and
Anne L.
Sollas1
1 Neurology Research Center, Helen Hayes Hospital, West
Haverstraw, New York 10993-1195, and 2 Departments of
Pharmacology and Neurology, Columbia University, College of Physicians
and Surgeons, New York, New York 10032
This study examined the acute actions of brain-derived neurotrophic
factor (BDNF) in the rat dentate gyrus after seizures, because previous
studies have shown that BDNF has acute effects on dentate granule cell
synaptic transmission, and other studies have demonstrated that BDNF
expression increases in granule cells after seizures.
Pilocarpine-treated rats were studied because they not only have
seizures and increased BDNF expression in granule cells, but they also
have reorganization of granule cell "mossy fiber" axons. This
reorganization, referred to as "sprouting," involves collaterals
that grow into novel areas, i.e., the inner molecular layer, where
granule cell and interneuron dendrites are located. Thus, this
animal model allowed us to address the effects of BDNF in the dentate
gyrus after seizures, as well as the actions of BDNF on mossy fiber
transmission after reorganization.
In slices with sprouting, BDNF bath application enhanced responses
recorded in the inner molecular layer to mossy fiber stimulation. Spontaneous bursts of granule cells occurred, and these were apparently generated at the site of the sprouted axon plexus. These effects were
not accompanied by major changes in perforant path-evoked responses or
paired-pulse inhibition, occurred only after prolonged (30-60 min)
exposure to BDNF, and were blocked by K252a.
The results suggest a preferential action of BDNF at mossy fiber
synapses, even after substantial changes in the dentate gyrus network.
Moreover, the results suggest that activation of trkB receptors could
contribute to the hyperexcitability observed in animals with sprouting.
Because human granule cells also express increased BDNF mRNA after
seizures, and sprouting can occur in temporal lobe epileptics, the
results may have implications for understanding temporal lobe epilepsy.
Key words:
neurotrophin; growth factor; hippocampus; epilepsy; glutamate; tyrosine kinase
Copyright © 1999 Society for Neuroscience 0270-6474/99/19135619-13$05.00/0
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