Seizure-like events in disinhibited ventral slices of adult rat hippocampus.

Epileptic discharges lasting 2-90 s, were studied in vitro in slices from the ventral hippocampus of adult rats, in which inhibition was blocked acutely with bicuculline methiodide (BMI, 5-30 microM) and potassium ([K(+)](o)) raised to 5 mM. These seizure-like events (SLEs) comprised three distinct phases, called here primary, secondary, and tertiary bursts. Primary bursts lasted 90-150 ms. Secondary bursts lasted a further 70-250 ms, comprising a short series of afterdischarges riding on the same depolarization as the primary burst. Finally a train of tertiary bursts started with a peak frequency of 5-10 Hz and could last >1 min. Slices from the ventral hippocampus showed significantly higher susceptibility to SLEs than did dorsal slices. SLEs proved sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. They were insensitive to N-methyl-D-aspartate (NMDA) receptor antagonists; 50 microl D-2-amino-5-phosphonopentanoic acid (D-AP5) did block the transient secondary bursts selectively. SLEs were restricted to the hippocampus proper even if the entorhinal cortex was present. Entorhinal bursts could last <2 s and were only coupled with hippocampal bursts in a minority of slices. Reentry of epileptic bursts occasionally occurred during interictal discharges, but not during the later stages of SLEs. Full-length SLEs always started in CA3 region and could be recorded in minislices containing CA3 plus dentate hilus. Ion-sensitive microelectrodes revealed that interictal discharges were followed by short (2-3 s) [K(+)](o) waves, peaking at approximately 7.5 mM. SLEs were always accompanied by increases in [K(+)](o) reaching approximately 8.5 mM at the start of tertiary bursts; [K(+)](o) then increased more slowly to a ceiling of 11-12 mM. After the end of each SLE, [K(+)](o) fell back to baseline within 10-15 s. SLEs were accompanied by significant increase in synaptic activity, compared with baseline and/or interictal activity, estimated by the variance of the intracellular signal in the absence of epileptic bursts and action potentials (0. 38 mV(2), compared with 0.13 mV(2), and 0.1 mV(2), respectively). No significant increases were observed in the interval preceding spontaneous interictal activity. These studies show that focal assemblies of hippocampal neurons, without long reentrant loops, are sufficient for the generation of SLEs. We propose that a key factor in the transition from interictal activity to SLEs is an increase in axonal and terminal excitability, resulting, at least in part, from elevations in [K(+)](o).

[1]  R. Traub,et al.  Model of synchronized epileptiform bursts induced by high potassium in CA3 region of rat hippocampal slice. Role of spontaneous EPSPs in initiation. , 1990, Journal of neurophysiology.

[2]  C. McBain,et al.  Hippocampal inhibitory neuron activity in the elevated potassium model of epilepsy. , 1994, Journal of neurophysiology.

[3]  J. Jefferys,et al.  Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions. , 1995, Physiological reviews.

[4]  J. L. Stringer,et al.  Functional anatomy of hippocampal seizures , 1991, Progress in Neurobiology.

[5]  W. W. Anderson,et al.  Seizure activity in vitro: a dual focus model , 1988, Epilepsy Research.

[6]  K. Abromeit Music Received , 2023, Notes.

[7]  F. Dudek,et al.  Synchronous neural afterdischarges in rat hippocampal slices without active chemical synapses. , 1982, Science.

[8]  H. Haas,et al.  Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission , 1982, Nature.

[9]  R. Dingledine,et al.  Role of extracellular space in hyperosmotic suppression of potassium-induced electrographic seizures. , 1989, Journal of neurophysiology.

[10]  U. Heinemann,et al.  Epileptiform activity in combined slices of the hippocampus, subiculum and entorhinal cortex during perfusion with low magnesium medium , 1986, Neuroscience Letters.

[11]  R. D. Traub,et al.  Models of the cellular mechanism underlying propagation of epileptiform activity in the CA2-CA3 region of the hippocampal slice , 1987, Neuroscience.

[12]  J. Mellanby,et al.  Limbic Epilepsy Induced by Tetanus Toxin: A Longitudinal Electroencephalographic Study , 1987, Epilepsia.

[13]  D. Prince,et al.  Penicillin‐induced epileptiform activity in the hippocampal in vitro preparation , 1977, Annals of neurology.

[14]  REGIONAL DIFFERENCES IN THE HIPPOCAMPUS OF THE CAT. II. PROJECTIONS OF THE DORSAL AND VENTRAL HIPPOCAMPUS. , 1964, Electroencephalography and clinical neurophysiology.

[15]  D. Mott,et al.  Hippocampal epileptiform activity induced by magnesium-free medium: differences between areas CA1 and CA2–3 , 1990, Epilepsy Research.

[16]  R. Dingledine,et al.  Potassium-induced spontaneous electrographic seizures in the rat hippocampal slice. , 1988, Journal of neurophysiology.

[17]  A. Williamson,et al.  A transient calcium‐dependent potassium component of the epileptiform burst after‐hyperpolarization in rat hippocampus. , 1988, Journal of Physiology.

[18]  W. W. Anderson,et al.  Regenerative, all-or-none electrographic seizures in the rat hippocampal slice in Mg-free and physiological medium , 1990, Brain Research.

[19]  Kenneth J. Smith,et al.  Internodal potassium currents can generate ectopic impulses in mammalian myelinated axons , 1993, Brain Research.

[20]  Karen L. Smith,et al.  Tetanus toxin-induced seizures in infant rats and their effects on hippocampal excitability in adulthood , 1995, Brain Research.

[21]  G. Golarai,et al.  Septotemporal variation of the supragranular projection of the mossy fiber pathway in the dentate gyrus of normal and kindled rats , 1992, Hippocampus.

[22]  H. Scharfman EPSPs of dentate gyrus granule cells during epileptiform bursts of dentate hilar "mossy" cells and area CA3 pyramidal cells in disinhibited rat hippocampal slices , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  R. Racine,et al.  Afterdischarge Thresholds and Kindling Rates in Dorsal and Ventral Hippocampus and Dentate Gyrus , 1977, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[24]  Cornelius Borck,et al.  On the Structure of Ictal Events in Vitro , 1996, Epilepsia.

[25]  C. Mitchell,et al.  Opioid-induced epileptiform bursting in hippocampal slices: higher susceptibility in ventral than dorsal hippocampus. , 1990, The Journal of pharmacology and experimental therapeutics.

[26]  D. Amaral,et al.  The three-dimensional organization of the hippocampal formation: A review of anatomical data , 1989, Neuroscience.

[27]  W. A. Wilson,et al.  Potassium-induced epileptiform activity in area CA3 varies markedly along the septotemporal axis of the rat hippocampus , 1986, Brain Research.

[28]  M. Avoli,et al.  Laminar organization of epileptiform discharges in the rat entorhinal cortex in vitro , 1998, The Journal of physiology.

[29]  E. Lothman Seizure circuits in the hippocampus and associated structures , 1994, Hippocampus.

[30]  Y. Yaari,et al.  The relationship between interictal and ictal paroxysms in an in vitro model of focal hippocampal epilepsy , 1988, Annals of neurology.

[31]  M. Hines,et al.  Axon terminal hyperexcitability associated with epileptogenesis in vitro. I. Origin of ectopic spikes. , 1993, Journal of neurophysiology.

[32]  L. R. Merlin Group I mGluR-mediated silent induction of long-lasting epileptiform discharges. , 1999, Journal of neurophysiology.

[33]  REGIONAL DIFFERENCES IN THE HIPPOCAMPUS OF THE CAT. I. SPECIFIC DISCHARGE PATTERNS OF THE DORSAL AND VENTRAL HIPPOCAMPUS AND THEIR ROLE IN GENERALIZED SEIZURES. , 1964, Electroencephalography and clinical neurophysiology.

[34]  E Neher,et al.  Measurement of extracellular potassium activity in cat cortex. , 1973, Brain research.

[35]  M. Avoli,et al.  CA3-Driven Hippocampal-Entorhinal Loop Controls Rather than Sustains In Vitro Limbic Seizures , 1997, The Journal of Neuroscience.

[36]  L. R. Merlin,et al.  Role of group I metabotropic glutamate receptors in the patterning of epileptiform activities in vitro. , 1997, Journal of neurophysiology.

[37]  J G Taylor Non-linear dynamics in neural networks. , 1994, Progress in brain research.

[38]  D. Spencer,et al.  Entorhinal‐Hippocampal Interactions in Medial Temporal Lobe Epilepsy , 1994, Epilepsia.

[39]  P. Somogyi,et al.  The hippocampal CA3 network: An in vivo intracellular labeling study , 1994, The Journal of comparative neurology.

[40]  R. Traub,et al.  Synaptic and intrinsic conductances shape picrotoxin‐induced synchronized after‐discharges in the guinea‐pig hippocampal slice. , 1993, The Journal of physiology.

[41]  R. Traub,et al.  Enhanced NMDA conductance can account for epileptiform activity induced by low Mg2+ in the rat hippocampal slice. , 1994, The Journal of physiology.

[42]  J. Swann,et al.  Penicillin-induced epileptogenesis in immature rat CA3 hippocampal pyramidal cells. , 1984, Brain research.

[43]  Wilkie A. Wilson,et al.  Magnesium-free medium activates seizure-like events in the rat hippocampal slice , 1986, Brain Research.

[44]  B. R. Sastry,et al.  Interactions among presynaptic fiber terminations in the CA1 region of the rat hippocampus , 1985, Neuroscience Letters.

[45]  R. Racine,et al.  Epileptiform burst responses in ventral vs dorsal hippocampal slices , 1985, Brain Research.

[46]  John Gordon Ralph Jefferys Mechanisms and experimental models of seizure generation. , 1998, Current opinion in neurology.

[47]  M. Avoli,et al.  Extracellular free potassium during synchronous activity induced by 4-aminopyridine in the juvenile rat hippocampus , 1994, Neuroscience Letters.

[48]  R. Traub,et al.  Simulations of epileptiform activity in the hippocampal CA3 region in vitro , 1994, Hippocampus.

[49]  M. Whittington,et al.  Epileptic activity outlasts disinhibition after intrahippocampal tetanus toxin in the rat. , 1994, The Journal of physiology.

[50]  R. Traub,et al.  Analysis of the propagation of disinhibition‐induced after‐discharges along the guinea‐pig hippocampal slice in vitro. , 1993, The Journal of physiology.

[51]  B. McNaughton,et al.  Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[52]  I. Módy,et al.  Epileptiform activity induced by lowering extracellular [Mg2+] in combined hippocampal-entorhinal cortex slices: Modulation by receptors for norepinephrine and N-methyl-d-aspartate , 1987, Epilepsy Research.

[53]  D. Prince,et al.  Extracellular potassium activity during epileptogenesis: a comparison between neocortex and hippocampus. , 1974, Transactions of the American Neurological Association.

[54]  P. Bergold,et al.  Requirement of protein synthesis for group I mGluR-mediated induction of epileptiform discharges. , 1998, Journal of neurophysiology.

[55]  J. Csicsvari,et al.  Epileptic afterdischarge in the hippocampal–entorhinal system: current source density and unit studies , 1997, Neuroscience.

[56]  Pankaj Sah,et al.  Ca2+-activated K+ currents in neurones: types, physiological roles and modulation , 1996, Trends in Neurosciences.

[57]  S. Spencer,et al.  Morphological Patterns of Seizures Recorded Intracranially , 1992, Epilepsia.

[58]  E. Barrett,et al.  Activation of internodal potassium conductance in rat myelinated axons. , 1993, The Journal of physiology.

[59]  J. Hablitz,et al.  Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors. , 1984, Journal of neurophysiology.

[60]  C. McBain,et al.  Hippocampal inhibitory neuron activity in the elevated potassium model of epilepsy. , 1995, Journal of neurophysiology.

[61]  C. Bernard,et al.  Model of local connectivity patterns in CA3 and CA1 areas of the hippocampus , 1994, Hippocampus.

[62]  J. Hablitz,et al.  Effect of APV and ketamine on epileptiform acitivity in the CA1 and CA3 regions of the hippocampus , 1990, Epilepsy Research.

[63]  J. Jefferys,et al.  Low‐calcium field burst discharges of CA1 pyramidal neurones in rat hippocampal slices. , 1984, The Journal of physiology.

[64]  B. Katz,et al.  Changes in end‐plate activity produced by pre‐synaptic polarization , 1954, The Journal of physiology.

[65]  P. Schwartzkroin,et al.  Somatostatin‐immunoreactivity in the hippocampus of mouse, rat, guinea pig, and rabbit , 1994, Hippocampus.

[66]  G. Sypert,et al.  Unidentified neuroglia potentials during propagated seizures in neocortex. , 1971, Experimental neurology.

[67]  R. Llinás,et al.  Role of the hippocampal-entorhinal loop in temporal lobe epilepsy: extra- and intracellular study in the isolated guinea pig brain in vitro , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[68]  L. R. Merlin,et al.  Role of metabotropic glutamate receptor subtypes in the patterning of epileptiform activities in vitro. , 1995, Journal of neurophysiology.

[69]  G. Aghajanian,et al.  Serotonin excitation of facial motoneurons: Receptor subtype characterization , 1990, Synapse.

[70]  John Gordon Ralph Jefferys,et al.  Synchronization of epileptiform bursts induced by 4-aminopyridine in the in vitro hippocampal slice preparation , 1990, Neuroscience Letters.

[71]  W. Müller,et al.  Picrotoxin- and 4-aminopyridine-induced activity in hilar neurons in the guinea pig hippocampal slice. , 1991, Journal of neurophysiology.

[72]  J N Turner,et al.  Diverse neuronal populations mediate local circuit excitation in area CA3 of developing hippocampus. , 1995, Journal of neurophysiology.

[73]  I. M. Gibson,et al.  Continuous recording of changes in membrane potential in mammalian cerebral tissues in vitro; recovery after depolarization by added substances , 1965, Journal of Physiology.

[74]  M. Mauk,et al.  Activity-evoked increases in extracellular potassium modulate presynaptic excitability in the CA1 region of the hippocampus. , 1987, Journal of neurophysiology.

[75]  A. Destexhe,et al.  Impact of spontaneous synaptic activity on the resting properties of cat neocortical pyramidal neurons In vivo. , 1998, Journal of neurophysiology.

[76]  Roland S. G. Jones Ictal epileptiform events induced by removal of extracellular magnesium in slices of entorhinal cortex are blocked by baclofen , 1989, Experimental Neurology.

[77]  M. Nelson,et al.  Inward Rectifier Potassium Channels in Resistance Arteries , 1994 .

[78]  B. Strowbridge,et al.  Transient potentiation of spontaneous EPSPs in rat mossy cells induced by depolarization of a single neurone. , 1996, The Journal of physiology.

[79]  S J Korn,et al.  Epileptiform burst activity induced by potassium in the hippocampus and its regulation by GABA-mediated inhibition. , 1987, Journal of neurophysiology.

[80]  M. Witter,et al.  Entorhinal-Hippocampal Interactions Revealed by Real-Time Imaging , 1996, Science.

[81]  Kl Smith,et al.  Localized excitatory synaptic interactions mediate the sustained depolarization of electrographic seizures in developing hippocampus , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[82]  Ard Teisman,et al.  Propagation of Epileptiform Activity During Development of Amygdala Kindling in Rats: Linear and Non‐linear Association Between lpsi‐ and Contralateral Sites , 1993, European Journal of Neuroscience.

[83]  R. Traub,et al.  Role of EPSPs in initiation of spontaneous synchronized burst firing in rat hippocampal neurons bathed in high potassium. , 1990, Journal of neurophysiology.

[84]  S. Stasheff,et al.  Axon terminal hyperexcitability associated with epileptogenesis in vitro. II. Pharmacological regulation by NMDA and GABAA receptors. , 1993, Journal of neurophysiology.

[85]  B H Gähwiler,et al.  Activity-dependent disinhibition. II. Effects of extracellular potassium, furosemide, and membrane potential on ECl- in hippocampal CA3 neurons. , 1989, Journal of neurophysiology.

[86]  R. Traub,et al.  Are there unifying principles underlying the generation of epileptic afterdischarges in vitro? , 1994, Progress in brain research.

[87]  R K Wong,et al.  Cellular basis of neuronal synchrony in epilepsy. , 1986, Advances in neurology.

[88]  M. Witter A survey of the anatomy of the hippocampal formation, with emphasis on the septotemporal organization of its intrinsic and extrinsic connections. , 1986, Advances in experimental medicine and biology.

[89]  R. Wong,et al.  Synchronized oscillations in hippocampal CA3 neurons induced by metabotropic glutamate receptor activation , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.