The Journal of Neurophysiology Vol. 84 No. 5 November 2000, pp. 2380-2389
Copyright ©2000 by the American Physiological Society
Modest Increase in Extracellular Potassium Unmasks Effect of
Recurrent Mossy Fiber Growth
Jeremy L.
Hardison,
Maxine M.
Okazaki, and
J. Victor
Nadler
Department of Pharmacology and Cancer Biology and Department of
Neurobiology, Duke University Medical Center, Durham, North Carolina
27710
Hardison, Jeremy L.,
Maxine M. Okazaki, and
J. Victor Nadler.
Modest Increase in Extracellular Potassium Unmasks Effect of
Recurrent Mossy Fiber Growth. J. Neurophysiol. 84: 2380-2389, 2000. The recurrent mossy fiber pathway
of the dentate gyrus expands dramatically in many persons with temporal
lobe epilepsy. The new connections among granule cells provide a novel
mechanism of synchronization that could enhance the participation of
these cells in seizures. Despite the presence of robust recurrent mossy fiber growth, orthodromic or antidromic activation of granule cells
usually does not evoke repetitive discharge. This study tested the
ability of modestly elevated
[K+]o, reduced
GABAA receptor-mediated inhibition and frequency
facilitation to unmask the effect of recurrent excitation. Transverse
slices of the caudal hippocampal formation were prepared from
pilocarpine-treated rats that either had or had not developed status
epilepticus with subsequent recurrent mossy fiber growth. During
superfusion with standard medium (3.5 mM K+),
antidromic stimulation of the mossy fibers evoked epileptiform activity
in 14% of slices with recurrent mossy fiber growth. This value
increased to ~50% when
[K+]o was raised to
either 4.75 or 6 mM. Addition of bicuculline (3 or 30 µM) to the
superfusion medium did not enhance the probability of evoking
epileptiform activity but did increase the magnitude of epileptiform
discharge if such activity was already present. (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (1 µM), which selectively activates type II metabotropic glutamate receptors present
on mossy fiber terminals, strongly depressed epileptiform responses.
This result implies a critical role for the recurrent mossy fiber
pathway. No enhancement of the epileptiform discharge occurred during
repetitive antidromic stimulation at frequencies of 0.2, 1, or 10 Hz.
In fact, antidromically evoked epileptiform activity became
progressively attenuated during a 10-Hz train. Antidromic stimulation
of the mossy fibers never evoked epileptiform activity in slices from
control rats under any condition tested. These results indicate that
even modest changes in
[K+]o dramatically affect
granule cell epileptiform activity supported by the recurrent mossy
fiber pathway. A small increase in
[K+]o reduces the amount
of recurrent mossy fiber growth required to synchronize granule cell
discharge. Block of GABAA receptor-mediated inhibition is less efficacious and frequency facilitation may not be a
significant factor.
