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The Journal of Neuroscience, August 15, 2000, 20(16):6144-6158
Granule-Like Neurons at the Hilar/CA3 Border after Status
Epilepticus and Their Synchrony with Area CA3 Pyramidal Cells:
Functional Implications of Seizure-Induced Neurogenesis
Helen E.
Scharfman1, 2,
Jeffrey H.
Goodman1, and
Anne L.
Sollas1
1 Center for Neural Recovery and Rehabilitation
Research, Helen Hayes Hospital, West Haverstraw, New York 10993-1195, and 2 Departments of Pharmacology and Neurology, Columbia
University, New York, New York 10032
A group of neurons with the characteristics of dentate gyrus
granule cells was found at the hilar/CA3 border several weeks after
pilocarpine- or kainic acid-induced status epilepticus. Intracellular
recordings from pilocarpine-treated rats showed that these
"granule-like" neurons were similar to normal granule cells (i.e.,
those in the granule cell layer) in membrane properties, firing
behavior, morphology, and their mossy fiber axon. However, in contrast
to normal granule cells, they were synchronized with spontaneous,
rhythmic bursts of area CA3 pyramidal cells that survived status
epilepticus. Saline-treated controls lacked the population of
granule-like cells at the hilar/CA3 border and CA3 bursts.
In rats that were injected after status epilepticus with
bromodeoxyuridine (BrdU) to label newly born cells, and also labeled for calbindin D28K (because it normally stains granule
cells), many double-labeled neurons were located at the hilar/CA3
border. Many BrdU-labeled cells at the hilar/CA3 border also were
double-labeled with a neuronal marker (NeuN). Taken together with the
recent evidence that granule cells that are born after seizures can
migrate into the hilus, the results suggest that some newly born
granule cells migrate as far as the CA3 cell layer, where they become integrated abnormally into the CA3 network, yet they retain granule cell intrinsic properties. The results provide insight into the physiological properties of newly born granule cells in the adult brain
and suggest that relatively rigid developmental programs set the
membrane properties of newly born cells, but substantial plasticity is
present to influence their place in pre-existing circuitry.
Key words:
epilepsy; plasticity; cell migration; dentate gyrus; kainic acid; pilocarpine
Copyright © 2000 Society for Neuroscience 0270-6474/00/20166144-15$05.00/0
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