Journal of Neurophysiology, Vol 71, Issue 4 1574-1585, Copyright © 1994 by APS

ARTICLES

Spontaneous interictal-like activity originates in multiple areas of the CA2-CA3 region of hippocampal slices

L. V. Colom and P. Saggau
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030.

1. The sites of origin of spontaneous interictal-like epileptiform activity in hippocampal slices from guinea pig, mouse, and rat were determined. A multisite fast optical recording technique using voltage-sensitive dyes and an array of 100 photodiodes was employed. The use of a low-magnification objective lens allowed the visualization of almost the entire transverse hippocampal slice. Three in vitro models of epilepsy were employed, utilizing different manipulations of the bath perfusion medium to induce epileptiform activity: 1) raising the external potassium (K+) concentration, 2) adding the potassium channel blocker 4-aminopyridine (4-AP), and 3) adding antagonists of gamma-aminobutyric acid-A (GABAA) receptors (bicuculline and picrotoxin, BIC-PTX). 2. Spontaneous epileptiform discharges were detected in each subfield of cornu ammonis (CA) but not in the dentate gyrus (DG) of each studied species. Preliminary experiments confirmed that interictal-like epileptiform activity originated in the CA2-CA3 region. Ictal-like activity was never observed in our experiments. 3. In the guinea pig, when GABAA antagonists were employed, the site of origin of spontaneous epileptiform discharges was consistently located in the CA2-CA3a region. When high K+ or 4-AP was used, this region was the most frequent site of origin. Subsequent epileptiform discharges with similar sites of origin occasionally invaded different areas of the CA2-CA3 region, revealing a variable area of occupance of epileptiform discharges. 4. In the mouse and rat, the site of origin of spontaneous discharges was invariably located in the CA3b-CA3c region independent of the epilepsy model. 5. In both the guinea pig and rat, when the CA2-CA3a region was surgically separated from the CA3b-CA3c region, independent discharges were observed in both regions. Areas that could generate discharges only under certain epileptogenic conditions were found in these species (potential sites of origin). Two independent sites of origin with different propagation patterns and area of occupance were occasionally observed within the CA2-CA3a region. 6. In the guinea pig, such lesions demonstrated that both regions can independently generate epileptiform discharges at different frequencies. When high K+ or 4-AP was employed, epileptiform activity was observed in both regions. Although BIC-PTX only generated discharges in the CA2-CA3a region, a subsequent increase in K+ induced additional discharges in the CA3b-CA3c region, revealing a potential site of origin. 7. In rat hippocampal slices with such lesions, spontaneous epileptiform discharges were observed in both CA2-CA3a and CA3b-CA3c region when 4-AP was employed.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				L. de Almeida, M. Idiart, and J. E. Lisman Memory retrieval time and memory capacity of the CA3 network: Role of gamma frequency oscillations Learn. Mem., November 15, 2007; 14(11): 795 - 806. [Abstract] [Full Text] [PDF]

				L. Wittner and R. Miles Factors defining a pacemaker region for synchrony in the hippocampus J. Physiol., November 1, 2007; 584(3): 867 - 883. [Abstract] [Full Text] [PDF]

				P. Y. Chang, P. E. Taylor, and M. B. Jackson Voltage Imaging Reveals the CA1 Region at the CA2 Border as a Focus for Epileptiform Discharges and Long-Term Potentiation in Hippocampal Slices J Neurophysiol, September 1, 2007; 98(3): 1309 - 1322. [Abstract] [Full Text] [PDF]

				D. F. de Sevilla, J. Garduno, E. Galvan, and W. Buno Calcium-Activated Afterhyperpolarizations Regulate Synchronization and Timing of Epileptiform Bursts in Hippocampal CA3 Pyramidal Neurons J Neurophysiol, December 1, 2006; 96(6): 3028 - 3041. [Abstract] [Full Text] [PDF]

				K. Jandova, D. Pasler, L. L. Antonio, C. Raue, S. Ji, M. Njunting, O. Kann, R. Kovacs, H.-J. Meencke, E. A. Cavalheiro, et al. Carbamazepine-resistance in the epileptic dentate gyrus of human hippocampal slices Brain, December 1, 2006; 129(12): 3290 - 3306. [Abstract] [Full Text] [PDF]

				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]

				J. Glykys and I. Mody Hippocampal Network Hyperactivity After Selective Reduction of Tonic Inhibition in GABAA Receptor {alpha}5 Subunit-Deficient Mice J Neurophysiol, May 1, 2006; 95(5): 2796 - 2807. [Abstract] [Full Text] [PDF]

				S. Bolea, J. V. Sanchez-Andres, X. Huang, and J.-y. Wu Initiation and Propagation of Neuronal Coactivation in the Developing Hippocampus J Neurophysiol, January 1, 2006; 95(1): 552 - 561. [Abstract] [Full Text] [PDF]

				N. Kang, J. Xu, Q. Xu, M. Nedergaard, and J. Kang Astrocytic Glutamate Release-Induced Transient Depolarization and Epileptiform Discharges in Hippocampal CA1 Pyramidal Neurons J Neurophysiol, December 1, 2005; 94(6): 4121 - 4130. [Abstract] [Full Text] [PDF]

				A. R. McQuiston and P. Saggau Mu-opioid Receptors Facilitate the Propagation of Excitatory Activity in Rat Hippocampal Area CA1 by Disinhibition of all Anatomical Layers J Neurophysiol, September 1, 2003; 90(3): 1936 - 1948. [Abstract] [Full Text] [PDF]

				V. I. Dzhala and K. J. Staley Transition from Interictal to Ictal Activity in Limbic Networks In Vitro J. Neurosci., August 27, 2003; 23(21): 7873 - 7880. [Abstract] [Full Text] [PDF]

				F.-C. Hsu and S. S. Smith Progesterone Withdrawal Reduces Paired-Pulse Inhibition in Rat Hippocampus: Dependence on GABAA Receptor alpha 4 Subunit Upregulation J Neurophysiol, January 1, 2003; 89(1): 186 - 198. [Abstract] [Full Text] [PDF]

				S. R. Sinha and P. Saggau Imaging of 4-AP-Induced, GABAA-Dependent Spontaneous Synchronized Activity Mediated by the Hippocampal Interneuron Network J Neurophysiol, July 1, 2001; 86(1): 381 - 391. [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.-y. Wu, L. Guan, and Y. Tsau Propagating Activation during Oscillations and Evoked Responses in Neocortical Slices J. Neurosci., June 15, 1999; 19(12): 5005 - 5015. [Abstract] [Full Text] [PDF]

				L. M. Grover and C. Yan Blockade of GABAA Receptors Facilitates Induction of NMDA Receptor-Independent Long-Term Potentiation J Neurophysiol, June 1, 1999; 81(6): 2814 - 2822. [Abstract] [Full Text] [PDF]

				P. Golshani and E. G. Jones Synchronized Paroxysmal Activity in the Developing Thalamocortical Network Mediated by Corticothalamic Projections and "Silent" Synapses J. Neurosci., April 15, 1999; 19(8): 2865 - 2875. [Abstract] [Full Text] [PDF]

				R. Demir, L. B. Haberly, and M. B. Jackson Sustained and Accelerating Activity at Two Discrete Sites Generate Epileptiform Discharges in Slices of Piriform Cortex J. Neurosci., February 15, 1999; 19(4): 1294 - 1306. [Abstract] [Full Text] [PDF]

				R. Demir, L. B. Haberly, and M. B. Jackson Voltage Imaging of Epileptiform Activity in Slices From Rat Piriform Cortex: Onset and Propagation J Neurophysiol, November 1, 1998; 80(5): 2727 - 2742. [Abstract] [Full Text] [PDF]