Journal of Neurophysiology, Vol 70, Issue 3 961-975, Copyright © 1993 by APS

ARTICLES

Axon terminal hyperexcitability associated with epileptogenesis in vitro. I. Origin of ectopic spikes

S. F. Stasheff, M. Hines and W. A. Wilson
Department of Pharmacology, Duke University Medical Center, Durham 27710.

1. Intracellular and extracellular recording techniques were used to study the increase in ectopic (i.e., nonsomatic) action-potential generation occurring among CA3 pyramidal cells during the kindling-like induction of electrographic seizures (EGSs) in this subpopulation of the hippocampal slice. Kindling-like stimulus trains (60 Hz, 2 s) were delivered to s. radiatum of CA3 at 10-min intervals. As EGSs developed, the frequency of ectopic firing increased markedly (by 10.33 +/- 3.29 spikes/min, mean +/- SE, P << 0.01). Several methods were applied to determine the initiation site for these action potentials within the cell (axons vs. dendrites). 2. Collision tests were conducted between known antidromic and orthodromic action potentials in CA3 cells to determine the critical period, c, for collision. Attempts were then made to collide ectopic spikes with known antidromic action potentials. At intervals less than c, ectopic spikes failed to collide with antidromic ones, in 5 of 10 cases. In these cells, this clearly indicates that the ectopic spikes were themselves of axonal origin. In the remaining five cases, ectopic spikes collided with antidromic action potentials at intervals approximately equal to c, most likely because of interactions within the complex system of recurrent axon collaterals in CA3. 3. Action potentials of CA3 pyramidal cells were simulated with the use of a compartmental computer model, NEURON. These simulations were based on prior models of CA3 pyramidal neurons and of the motoneuron action potential. Simulated action potentials generated in axonal compartments possessed a prominent inflection on their rising phase (IS-SD break), which was difficult to appreciate in those spikes generated in somatic or dendritic compartments. 4. An analysis of action potentials recorded experimentally from CA3 pyramidal cells also showed that antidromic spikes possess a prominent IS-SD break that is not present in orthodromic spikes. In addition to identified antidromic action potentials, ectopic spikes also possess such an inflection. Together with the predictions of computer simulations, this analysis also indicates that ectopic spikes originate in the axons of CA3 cells. 5. Tetrodotoxin (TTX, 50 microM) was locally applied by pressure injection while monitoring ectopic spike activity. Localized application of TTX to regions of the slice that could include the axons but not the dendrites of recorded cells abolished or markedly reduced the frequency of ectopic spikes (n = 5), further confirming the hypothesis that these action potentials arise from CA3 axons.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				T. Fellin, M. Gomez-Gonzalo, S. Gobbo, G. Carmignoto, and P. G. Haydon Astrocytic Glutamate Is Not Necessary for the Generation of Epileptiform Neuronal Activity in Hippocampal Slices J. Neurosci., September 6, 2006; 26(36): 9312 - 9322. [Abstract] [Full Text] [PDF]

				Y. Fujiwara-Tsukamoto, Y. Isomura, and M. Takada Comparable GABAergic Mechanisms of Hippocampal Seizurelike Activity in Posttetanic and Low-Mg2+ Conditions J Neurophysiol, March 1, 2006; 95(3): 2013 - 2019. [Abstract] [Full Text] [PDF]

				H. Li, A. E. Bandrowski, and D. A. Prince Cortical Injury Affects Short-Term Plasticity of Evoked Excitatory Synaptic Currents J Neurophysiol, January 1, 2005; 93(1): 146 - 156. [Abstract] [Full Text] [PDF]

				M. Vreugdenhil, E. Bracci, and J. G. R. Jefferys Layer-specific pyramidal cell oscillations evoked by tetanic stimulation in the rat hippocampal area CA1 in vitro and in vivo J. Physiol., January 1, 2005; 562(1): 149 - 164. [Abstract] [Full Text] [PDF]

				Y. Schiller Activation of a Calcium-Activated Cation Current During Epileptiform Discharges and Its Possible Role in Sustaining Seizure-Like Events in Neocortical Slices J Neurophysiol, August 1, 2004; 92(2): 862 - 872. [Abstract] [Full Text] [PDF]

				Y. Fujiwara-Tsukamoto, Y. Isomura, K. Kaneda, and M. Takada Synaptic interactions between pyramidal cells and interneurone subtypes during seizure-like activity in the rat hippocampus J. Physiol., June 15, 2004; 557(3): 961 - 979. [Abstract] [Full Text] [PDF]

				Y. Isomura, Y. Fujiwara-Tsukamoto, and M. Takada Glutamatergic Propagation of GABAergic Seizure-Like Afterdischarge in the Hippocampus In Vitro J Neurophysiol, October 1, 2003; 90(4): 2746 - 2751. [Abstract] [Full Text] [PDF]

				V. Santhakumar, J. Voipio, K. Kaila, and I. Soltesz Post-Traumatic Hyperexcitability Is Not Caused by Impaired Buffering of Extracellular Potassium J. Neurosci., July 2, 2003; 23(13): 5865 - 5876. [Abstract] [Full Text] [PDF]

				R. Kohling, M. Vreugdenhil, E. Bracci, and J. G. R. Jefferys Ictal Epileptiform Activity Is Facilitated by Hippocampal GABAA Receptor-Mediated Oscillations J. Neurosci., September 15, 2000; 20(18): 6820 - 6829. [Abstract] [Full Text] [PDF]

				J. L. Calton, M.-H. Kang, W. A. Wilson, and S. D. Moore NMDA-Receptor-Dependent Synaptic Activation of Voltage-Dependent Calcium Channels in Basolateral Amygdala J Neurophysiol, February 1, 2000; 83(2): 685 - 692. [Abstract] [Full Text] [PDF]

				C. Borck and J. G. R. Jefferys Seizure-Like Events in Disinhibited Ventral Slices of Adult Rat Hippocampus J Neurophysiol, November 1, 1999; 82(5): 2130 - 2142. [Abstract] [Full Text] [PDF]

				F. E. Jensen, C. Wang, C. E. Stafstrom, Z. Liu, C. Geary, and M. C. Stevens Acute and Chronic Increases in Excitability in Rat Hippocampal Slices After Perinatal Hypoxia In Vivo J Neurophysiol, January 1, 1998; 79(1): 73 - 81. [Abstract] [Full Text] [PDF]

				M. E. Barish, M. Ichikawa, T. Tominaga, G. Matsumoto, and T. Iijima Enhanced Fast Synaptic Transmission and a Delayed Depolarization Induced by Transient Potassium Current Blockade in Rat Hippocampal Slice as Studied by Optical Recording J. Neurosci., September 15, 1996; 16(18): 5672 - 5687. [Abstract] [Full Text] [PDF]