Increased dendritic excitability in hippocampal ca1 in vivo in the kainic acid model of temporal lobe epilepsy: a study using current source density analysis

We used kainic acid in rats as an animal model of temporal lobe epilepsy, and studied the synaptic transmission in hippocampal subfield CA1 of urethane-anesthetized rats in vivo. Dendritic currents were revealed by field potential mapping, using a single micropipette or a 16-channel silicon probe, followed by current source density analysis. We found that the population excitatory postsynaptic potentials in the basal dendrites and distal apical dendrites of CA1 were increased in kainate-treated as compared with control rats following paired-pulse, but not single-pulse, stimulation of CA3b or medial perforant path. In contrast, the trisynaptic midapical dendritic response in CA1 following medial perforant path stimulation was decreased in kainate-treated as compared with control rats. Increased coupling between excitatory postsynaptic potential and the population spike in CA1 was found after kainate seizures. Short-latency, presumably monosynaptic CA1 population spikes following medial perforant path stimulation was found in kainate-treated but not control rats. An enhancement of dendritic excitability was evidenced by population spikes that invaded into or originated from the distal apical dendrites of CA1 in kainate-treated but not control rats. Reverberation of hippocampo-entorhinal activity was evidenced by recurrent excitation of CA1 following CA3b stimulation in kainate-treated but not control rats. Blockade of inhibition by intraventricularly administered bicuculline induced excitatory potentials in CA1 that were stronger and more prolonged in kainate-treated than control rats. The bicuculline-induced excitation was mainly blocked by non-N-methyl-D-aspartate receptor antagonists. We conclude that kainate seizures induced disinhibition in CA1 that unveiled excitation at the basal and distal apical dendrites, resulting in enhancement of the direct entorhinal cortex to CA1 input and reverberations via the hippocampo-entorhinal loop. These changes in the output of the hippocampus from CA1 are likely detrimental to the behavioral functions of the hippocampus and they may contribute to increased seizure susceptibility after kainate seizures.

[1]  F. Dudek,et al.  Spontaneous and stimulation-induced synchronized burst afterdischarges in the isolated CA1 of kainate-treated rats. , 1996, Journal of neurophysiology.

[2]  M. Vreugdenhil,et al.  Kindling-induced long-lasting enhancement of calcium current in hippocampal CA1 area of the rat: Relation to calcium-dependent inactivation , 1994, Neuroscience.

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

[4]  M. Witter,et al.  Anatomical Organization of the Parahippocampal‐Hippocampal Network , 2000, Annals of the New York Academy of Sciences.

[5]  H. Wheal,et al.  The contribution of non-NMDA and NMDA receptors to graded bursting activity in the CA1 region of the hippocampus in a chronic model of epilepsy. , 1991, Canadian journal of physiology and pharmacology.

[6]  R K Wong,et al.  Synchronized burst discharge in disinhibited hippocampal slice. I. Initiation in CA2-CA3 region. , 1983, Journal of neurophysiology.

[7]  Christophe Bernard,et al.  Newly formed excitatory pathways provide a substrate for hyperexcitability in experimental temporal lobe epilepsy , 1999, The Journal of comparative neurology.

[8]  D. Coulter,et al.  Differential epilepsy-associated alterations in postsynaptic GABA(A) receptor function in dentate granule and CA1 neurons. , 1997, Journal of neurophysiology.

[9]  C. Nicholson,et al.  Experimental optimization of current source-density technique for anuran cerebellum. , 1975, Journal of neurophysiology.

[10]  M. Vreugdenhil,et al.  Calcium currents in pyramidal CA1 neurons in vitro after kindling epileptogenesis in the hippocampus of the rat , 1996, Neuroscience.

[11]  D. Coulter,et al.  Selective changes in single cell GABAA receptor subunit expression and function in temporal lobe epilepsy , 1998, Nature Medicine.

[12]  J. Nadler,et al.  Recurrent mossy fiber pathway in rat dentate gyrus: synaptic currents evoked in presence and absence of seizure-induced growth. , 1999, Journal of neurophysiology.

[13]  E. Lothman,et al.  Dormancy of inhibitory interneurons in a model of temporal lobe epilepsy. , 1993, Science.

[14]  H. Wheal,et al.  Changes in parvalbumin-immunoreactive neurons in the rat hippocampus following a kainic acid lesion , 1993, Neuroscience Letters.

[15]  K. Wu,et al.  Enhanced but fragile inhibition in the dentate gyrus in vivo in the kainic acid model of temporal lobe epilepsy: a study using current source density analysis , 2001, Neuroscience.

[16]  D. Johnston,et al.  Electrical and calcium signaling in dendrites of hippocampal pyramidal neurons. , 1998, Annual review of physiology.

[17]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[18]  L. W. Leung,et al.  Field Potentials in the Central Nervous System , 1990 .

[19]  Y. Ben-Ari,et al.  Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy , 2001, Nature Neuroscience.

[20]  T. W. Berger,et al.  Spatial Distribution of Potentiated Synapses in Hippocampus: Dependence on Cellular Mechanisms and Network Properties , 1998, The Journal of Neuroscience.

[21]  R. Racine,et al.  Nerve Growth Factor Accelerates Seizure Development, Enhances Mossy Fiber Sprouting, and Attenuates Seizure-Induced Decreases in Neuronal Density in the Kindling Model of Epilepsy , 1997, The Journal of Neuroscience.

[22]  C. Bernard,et al.  Plasticity of AMPA and NMDA receptor-mediated epileptiform activity in a chronic model of temporal lobe epilepsy , 1995, Epilepsy Research.

[23]  F. Dudek,et al.  Short- and long-term changes in CA1 network excitability after kainate treatment in rats. , 2001, Journal of neurophysiology.

[24]  H. Wheal,et al.  Long-term loss of paired pulse inhibition in the kainic acid-lesioned hippocampus of the rat , 1989, Neuroscience.

[25]  J. DeFelipe,et al.  Deficit of quantal release of GABA in experimental models of temporal lobe epilepsy , 1999, Nature Neuroscience.

[26]  I. Módy,et al.  Lasting potentiation of inhibition is associated with an increased number of gamma-aminobutyric acid type A receptors activated during miniature inhibitory postsynaptic currents. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[27]  L. Leung,et al.  Difference in LTP at basal and apical dendrites of CA1 pyramidal neurons in urethane-anesthetized rats , 1995, Brain Research.

[28]  Dichen Zhao,et al.  Effects of hippocampal kindling on paired-pulse response in CA1 in vitro , 1991, Brain Research.

[29]  J. Lacaille,et al.  Cell-specific alterations in synaptic properties of hippocampal CA1 interneurons after kainate treatment. , 1998, Journal of neurophysiology.

[30]  O Herreras,et al.  Propagating dendritic action potential mediates synaptic transmission in CA1 pyramidal cells in situ. , 1990, Journal of neurophysiology.

[31]  H. V. Wheal,et al.  Extracellular studies on the role of N-methyl-d-aspartate receptors in epileptiform activity recorded from the kainic acid-lesioned hippocampus , 1986, Neuroscience Letters.

[32]  J. Lacaille,et al.  Alterations of perisomatic GABA synapses on hippocampal CA1 inhibitory interneurons and pyramidal cells in the kainate model of epilepsy , 1999, Neuroscience.

[33]  R. Schwarcz,et al.  Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  K. Wu,et al.  Functional interconnections between CA3 and the dentate gyrus revealed by current source density analysis , 1998, Hippocampus.

[35]  H. Wheal,et al.  Loss of inhibition in the CA1 region of the kainic acid lesioned hippocampus is not associated with changes in postsynaptic responses to GABA , 1986, Brain Research.

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

[37]  J. L. Stringer,et al.  Reverberatory seizure discharges in hippocampal-parahippocampal circuits , 1992, Experimental Neurology.

[38]  B. Lancaster,et al.  Intracellular electrophysiology of CA1 pyramidal neurones in slices of the kainic acid lesioned hippocampus of the rat , 2004, Experimental Brain Research.

[39]  R. Cannon,et al.  Pro-epileptic changes in synaptic function can be accompanied by pro-epileptic changes in neuronal excitability , 1998, Trends in Neurosciences.

[40]  Peter Somogyi,et al.  Increased number of synaptic GABAA receptors underlies potentiation at hippocampal inhibitory synapses , 1998, Nature.

[41]  K. J. Canning,et al.  Entorhinal inputs to hippocampal CA1 and dentate gyrus in the rat: a current-source-density study. , 1995, Journal of neurophysiology.

[42]  R. Racine,et al.  The effects of kindling on GABA-Mediated inhibition in the dentate gyrus of the rat. I. Paired-pulse depression , 1982, Brain Research.

[43]  F. Kloosterman,et al.  Physiology of the Entorhinal and Perirhinal Projections to the Hippocampus Studied by Current Source Density Analysis , 2000, Annals of the New York Academy of Sciences.

[44]  PA Schwartzkroin,et al.  Interneurons and inhibition in the dentate gyrus of the rat in vivo , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  J. Lacaille,et al.  Axonal Sprouting of CA1 Pyramidal Cells in Hyperexcitable Hippocampal Slices of Kainate‐treated Rats , 1996, The European journal of neuroscience.

[46]  B. Longo,et al.  Supragranular mossy fiber sprouting is not necessary for spontaneous seizures in the intrahippocampal kainate model of epilepsy in the rat , 1998, Epilepsy Research.

[47]  M. Vreugdenhil,et al.  Sodium currents in isolated rat CA1 neurons after kindling epileptogenesis , 1998, Neuroscience.

[48]  D A Turner,et al.  Excitatory synaptic potentials in kainic acid-denervated rat CA1 pyramidal neurons , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[49]  G. Sperk,et al.  GABAA receptor subunits in the rat hippocampus III: altered messenger RNA expression in kainic acid-induced epilepsy , 1997, Neuroscience.

[50]  P. Saggau,et al.  Presynaptic inhibition of elicited neurotransmitter release , 1997, Trends in Neurosciences.

[51]  R. Sutherland,et al.  Long-Lasting Behavioral and Electrophysiological Effects Induced by Partial Hippocampal Kindling , 1998 .

[52]  T. Freund,et al.  Differences between Somatic and Dendritic Inhibition in the Hippocampus , 1996, Neuron.

[53]  C. Wilson,et al.  Paired pulse suppression and facilitation in human epileptogenic hippocampal formation , 1998, Epilepsy Research.

[54]  D. Debanne,et al.  Lesion-induced axonal sprouting and hyperexcitability in the hippocampus in vitro: Implications for the genesis of posttraumatic epilepsy , 1997, Nature Medicine.

[55]  Nace L. Golding,et al.  Dendritic Sodium Spikes Are Variable Triggers of Axonal Action Potentials in Hippocampal CA1 Pyramidal Neurons , 1998, Neuron.

[56]  T. Bliss,et al.  Lamellar organization of hippocampal pathways. , 1971, Experimental brain research.

[57]  H. Wheal,et al.  Ultrastructure of parvalbumin-immunoreactive neurons in the CA1 area of the rat hippocampus following a kainic acid injection , 1994, Acta Neuropathologica.

[58]  F. Dudek,et al.  Excitatory synaptic input to granule cells increases with time after kainate treatment. , 2001, Journal of neurophysiology.

[59]  G. Golarai,et al.  Functional alterations in the dentate gyrus after induction of long-term potentiation, kindling, and mossy fiber sprouting. , 1996, Journal of neurophysiology.

[60]  D. Amaral,et al.  Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat , 1990, The Journal of comparative neurology.

[61]  W. Regehr,et al.  Short-term synaptic plasticity. , 2002, Annual review of physiology.

[62]  F. Kloosterman,et al.  Apical and basal orthodromic population spikes in hippocampal CA1 in vivo show different origins and patterns of propagation. , 2001, Journal of neurophysiology.

[63]  R. Racine,et al.  Changes in inhibitory processes in the hippocampus following recurrent seizures induced by systemic administration of kainic acid , 1991, Brain Research.

[64]  P. Schwartzkroin,et al.  Inhibition in kainate-lesioned hyperexcitable hippocampi: physiologic, autoradiographic, and immunocytochemical observations , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[65]  C. Cotman,et al.  Loss and reacquisition of hippocampal synapses after selective destruction of CA3–CA4 afferents with kainic acid , 1980, Brain Research.

[66]  J. Lacaille,et al.  Monosynaptic GABA-mediated inhibitory postsynaptic potentials in ca1 pyramidal cells of hyperexcitable hippocampal slices from kainic acid-treated rats , 1993, Neuroscience.

[67]  W. N. Ross,et al.  IPSPs modulate spike backpropagation and associated [Ca2+]i changes in the dendrites of hippocampal CA1 pyramidal neurons. , 1996, Journal of neurophysiology.

[68]  J. Wadia,et al.  Kindling induces an asymmetric enhancement of N-type Ca2+ channel density in the dendritic fields of the rat hippocampus , 1999, Neuroscience Letters.

[69]  T. Otis.  Lasting potentiation of inhibition is associated with an increased number of GABA_A receptors activated during miniature inhibitory postsynaptic currents , 1994 .

[70]  F. Dudek,et al.  Network properties of the dentate gyrus in epileptic rats with hilar neuron loss and granule cell axon reorganization. , 1997, Journal of neurophysiology.

[71]  J. E. Franck,et al.  Do kainate-lesioned hippocampi become epileptogenic? , 1985, Brain Research.

[72]  Recovery of function following injections of kainic acid: Behavioral, electrophysiological and neuroanatomical correlates , 1984, Brain Research.

[73]  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.

[74]  T. Bliss,et al.  Lamellar organization of hippocampal excitatory pathways , 1971, Experimental Brain Research.

[75]  T. Kaibara,et al.  Basal versus apical dendritic long-term potentiation of commissural afferents to hippocampal CA1: a current-source density study , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.