Journal of Neurophysiology, Vol 72, Issue 4 1874-1884, Copyright © 1994 by APS

ARTICLES

Endogenous bursts underlie seizurelike activity in solitary excitatory hippocampal neurons in microcultures

M. M. Segal
Department of Neurology, Children's Hospital, Boston, Massachusetts 02115.

1. I compared the relative contributions of synaptic potentials and endogenous bursting to seizurelike activity in a simple model system. The system consisted of a solitary excitatory hippocampal rat neuron in a microculture. Each solitary excitatory neuron was grown in kynurenate and elevated magnesium and had excitatory autapses. 2. In normal physiological solution most neurons displayed the characteristic type of interictal epileptiform activity, the paroxysmal depolarizing shift (PDS). A minority of neurons displayed ictuslike epileptiform activity consisting of runs of PDSs with a sustained neuronal depolarization. 3. I analyzed the synaptic and nonsynaptic components underlying these forms of epileptiform activity. The synaptic and calcium current components of the epileptiform activity were removed by using a "synapse blocking solution" in which calcium was replaced with magnesium, and glutamate receptor activity was blocked using the glutamate antagonists 2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione. Neurons that had only PDSs in normal physiological solution typically displayed only one or two action potentials in this synapse blocking solution. In contrast, neurons that had sustained depolarizations in normal physiological solution generally displayed bursts of action potentials in the synapse blocking solution, and some of the bursts had plateau depolarizations that lasted as long as several seconds. 4. The seconds-long endogenous plateau depolarizations were suppressed by tetrodotoxin, indicating involvement of persistent sodium currents. 5. The plateau depolarizations were shortened or abolished by 8 microM phenytoin, but there was only a small effect of phenytoin on nonplateau sustained repetitive firing of action potentials. 6. Elevation of extracellular potassium to 8 mM typically intensified the endogenous activity, usually converting action potential bursts to bursts with plateaus. 7. This study demonstrates that a sodium-dependent endogenous bursting underlies ictuslike epileptiform activity in this model system of seizurelike activity. The ability of phenytoin to attenuate this endogenous bursting suggests that a similar mechanism might underlie epileptiform bursting in less reduced systems such as brain slices or intact animals.

This article has been cited by other articles:

				C. G. Vanoye, C. Lossin, T. H. Rhodes, and A. L. George Jr. Single-channel Properties of Human NaV1.1 and Mechanism of Channel Dysfunction in SCN1A-associated Epilepsy J. Gen. Physiol., December 27, 2005; 127(1): 1 - 14. [Abstract] [Full Text] [PDF]

				J. P Meeks, X. Jiang, and S. Mennerick Action potential fidelity during normal and epileptiform activity in paired soma-axon recordings from rat hippocampus J. Physiol., July 15, 2005; 566(2): 425 - 441. [Abstract] [Full Text] [PDF]

				M. Bikson, P. J. Hahn, J. E. Fox, and J. G.R. Jefferys Depolarization Block of Neurons During Maintenance of Electrographic Seizures J Neurophysiol, October 1, 2003; 90(4): 2402 - 2408. [Abstract] [Full Text] [PDF]

				J. Magistretti and A. Alonso Fine Gating Properties of Channels Responsible for Persistent Sodium Current Generation in Entorhinal Cortex Neurons J. Gen. Physiol., November 25, 2002; 120(6): 855 - 873. [Abstract] [Full Text] [PDF]

				W. C. Stacey and D. M. Durand Noise and Coupling Affect Signal Detection and Bursting in a Simulated Physiological Neural Network J Neurophysiol, November 1, 2002; 88(5): 2598 - 2611. [Abstract] [Full Text] [PDF]

				J. Magistretti, D. S. Ragsdale, and A. Alonso High Conductance Sustained Single-Channel Activity Responsible for the Low-Threshold Persistent Na+ Current in Entorhinal Cortex Neurons J. Neurosci., September 1, 1999; 19(17): 7334 - 7341. [Abstract] [Full Text] [PDF]

				S. Taverna, G. Sancini, M. Mantegazza, S. Franceschetti, and G. Avanzini Inhibition of Transient and Persistent Na+ Current Fractions by the New Anticonvulsant Topiramate J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 960 - 968. [Abstract] [Full Text]

				T. P. Norekian GABAergic Excitatory Synapses and Electrical Coupling Sustain Prolonged Discharges in the Prey Capture Neural Network of Clione limacina J. Neurosci., March 1, 1999; 19(5): 1863 - 1875. [Abstract] [Full Text] [PDF]

				M. M. Segal and A. F. Douglas Late Sodium Channel Openings Underlying Epileptiform Activity Are Preferentially Diminished by the Anticonvulsant Phenytoin J Neurophysiol, June 1, 1997; 77(6): 3021 - 3034. [Abstract] [Full Text] [PDF]

				S. Selig, H. G. W. Lidov, S. A. Bruno, M. M. Segal, and L. M. Kunkel Molecular characterization of Br-cadherin, a developmentally regulated, brain-specific cadherin PNAS, March 18, 1997; 94(6): 2398 - 2403. [Abstract] [Full Text] [PDF]

				Z.-H. Pan, M. M. Segal, and S. A. Lipton Nitric oxide-related species inhibit evoked neurotransmission but enhance spontaneous miniature synaptic currents in central neuronal cultures PNAS, December 24, 1996; 93(26): 15423 - 15428. [Abstract] [Full Text] [PDF]

				G. Chen and A. N. van den Pol Multiple NPY Receptors Coexist in Pre- and Postsynaptic Sites: Inhibition of GABA Release in Isolated Self-Innervating SCN Neurons J. Neurosci., December 1, 1996; 16(23): 7711 - 7724. [Abstract] [Full Text] [PDF]

				D. D. Fraser and B. A. MacVicar Cholinergic-Dependent Plateau Potential in Hippocampal CA1 Pyramidal Neurons J. Neurosci., July 1, 1996; 16(13): 4113 - 4128. [Abstract] [Full Text] [PDF]

				J. Lubke, H. Markram, M. Frotscher, and B. Sakmann Frequency and Dendritic Distribution of Autapses Established by Layer 5 Pyramidal Neurons in the Developing Rat Neocortex: Comparison with Synaptic Innervation of Adjacent Neurons of the Same Class J. Neurosci., May 15, 1996; 16(10): 3209 - 3218. [Abstract] [Full Text] [PDF]