Mechanisms of Kindling: A Speculative Hypothesis
Published 1 January 1988
James O McNamara, Douglas W. Bonhaus, Cheolsu Shin
Citations5
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Abstract
The initial description of the kindling phenomenon was reported by Graham Goddard and his colleagues in 1967 (1). Kindling has subsequently become the most extensively studied animal model of epilepsy in the ensuing twenty years.
Keywords
MedicineNeuroscienceBiochemistry, Genetics and Molecular Biology
Electroencephalography and Clinical NeurophysiologyModification of seizure activity by electrical stimulation: II. Motor seizure
7,160 Citations1972Ronald J. Racine
It was found that the development of motor seizures by stimulation of the amygdala resulted in an increased ability of the contralateral amygdala, and the septal area, but not of the hippocampus, to drive motor seizures when stimulated (“transfer”).
Experimental NeurologyA permanent change in brain function resulting from daily electrical stimulation
3,055 Citations1969Graham V. Goddard, Dan McIntyre +1 more
High-intensity stimulation studies revealed that the development of convulsions was not based simply on threshold reduction, but involved complex reorganization of function.
The Journal of Comparative NeurologyTopographic organization of the projections from the entorhinal area to the hippocampal formation of the rat
876 Citations1976Oswald Steward
The present study re‐examines, with autoradiographic methods, the pattern of termination of fibers originating from various medio‐lateral divisions of the entorhinal cortex on dentate granule cells and on hippocampa pyramidal cells of the rat.
NatureDevelopment of Epileptic Seizures through Brain Stimulation at Low Intensity
858 Citations1967Graham V. Goddard
This note does not debate this temporary elevation of convulsion threshold but rather emphasizes an equally important phenomenon in which, over a longer period of time, the convulsive threshold is reduced.
ScienceSubstantia Nigra: Site of Anticonvulsant Activity Mediated by γ-Aminobutyric Acid
599 Citations1982Michael J. Iadarola, Karen Gale
Local injection of GABA agonists into the midbrain provided seizure protection without a widespread augmentation of GABA-mediated activity throughout the brain and without impairing either alertness or motor function.
Brain ResearchLong-term potentiation phenomena in the rat limbic forebrain
555 Citations1983R. Racine, Norton W. Milgram +1 more
The result indicates that the potentiation produced by kindling may be based upon the same mechanism as the LTP effect, and the effect of this potentiation on subsequent tests of short-term and long-term potentiation.
Brain ResearchLong-term potentiation of the perforant path-granule cell synapse in the rat hippocampus
505 Citations1975Robert M. Douglas, Graham V. Goddard
The results imply that the efficiency of synaptic transmission in the perforant path-granule cell synapse can be modified.
NeurosurgeryKindling
480 Citations1978Ronald J. Racine
The kindling phenomenon is a progressive increase in the strength of epileptiform activity evoked by spaced (in time) and repeated electrical stimulation of certain brain structures that is clear that the kindling effect is not due to any type of gross tissue damage.
The Journal of Comparative NeurologyCrossed connections of the substantia nigra in the rat
435 Citations1982Charles R. Gerfen, William A. Staines +2 more
The existence of crossed multisynaptic pathways that allow for the interdependent control of activity in one substantia nigra and its contralateral counterpart has been inferred from a number of recent biochemical and neurophysiological investigations and prompted a reexamination of the connections of the substantia Nigra with an emphasis on crossed inputs to and crossed projections from that nucleus.
The Journal of PhysiologyInvolvement of N‐methyl‐D‐aspartate receptors in epileptiform bursting in the rat hippocampal slice.
354 Citations1986Raymond Dingledine, Mary Hynes +1 more
It is proposed that, under normal (non‐epileptic) physiological conditions, the balance between synaptic inhibition mediated by GABA receptors and synaptic excitation mediated by NMDA receptors may modulate the excitability of pyramidal cell dendrites.
Brain ResearchThe effects of kindling on GABA-Mediated inhibition in the dentate gyrus of the rat. I. Paired-pulse depression
332 Citations1983LAWRENCE TUFF, R. Racine +1 more
Results indicated that kindling increased, rather than reduced, inhibition in the dentate gyrus, suggesting an enhanced resistance to inhibitory failure.
NeurologyGeneralized convulsive seizures induced by daily electrical stimulation of the amygdala in cats
321 Citations1974Jun Wada, MITSUMOTO SATA
Seizure development was characterized by early distant propagation, amplitude growth of after-discharge, and development of interictal discharge along the ex-trapyramidal pathways through three distinct steps in which the mid-brain reticular formation plays a vital role in producing widespread secondary alteration and reorganization of brain function.
The Journal of Comparative NeurologyAn autoradiographic study of the efferent connections of the entorhinal cortex in the rat
308 Citations1981J. Michael Wyss
NatureAspartate and glutamate as possible transmitters of excitatory hippocampal afferents
303 Citations1976J. Victor Nadler, K Vaca +3 more
These phenomena must involve profound alterations of synaptic biochemistry, but the requisite biochemical studies cannot be performed until the transmitters used by these inputs are known.
Journal of NeuroscienceEvidence implicating substantia nigra in regulation of kindled seizure threshold
301 Citations1984JO McNamara, M T Galloway +2 more
The suppression of limbic seizures indicates that this brainstem nucleus can regulate the intrinsic neuronal excitability of hemispheric sites and is interpreted to indicate that the SN is the site at which the GABA agonists and lesions act to raise the threshold for kindled seizures.
Brain ResearchImmunocytochemical localization of glutamate decarboxylase in rat substantia nigra
270 Citations1976Charles E. Ribak, James E. Vaughn +3 more
Electron microscopic studies revealed that most of the axon terminals in the substantia nigra were filled with GAD-positive reaction product and formed both axodendritic and axosomatic synapses, providing another example in the vertebrate central nervous system where Golgi I projection neurons are inhibitory and use GABA as their neurotransmitter.
Journal of NeurophysiologyEpileptiform burst activity induced by potassium in the hippocampus and its regulation by GABA-mediated inhibition
267 Citations1987Stephen J. Korn, J.L. Giacchino +2 more
It is hypothesize that high potassium induces a rise in intracellular chloride concentration, possibly by activating an inward KCl pump or by a passive Donnan effect, which results in a decreased IPSP amplitude.
Journal of NeurophysiologyNeuronal transmission through hippocampal pathways dependent on behavior
264 Citations1978Jonathan Winson, Charles Abzug
The results are interpreted as suggesting that the granule cell membranes in the DG are relatively hyperpolarized during SAL compared with SWS as the result of either tonic excitatory bombardment occurring during SWS or tonic inhibitory bombardment during SAL.
Annals of NeurologyAnatomical correlates of electrical and behavioral events related to amygdaloid kindling
248 Citations1978Jerome Engel, Leslie Wolfson +1 more
It is suggested that three discrete anatomical systems underlie the generation of partial seizures, generalized motor seizures, and local afterdischarge in rats.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences NeurologiquesDoes the Engram of Kindling Model the Engram of Normal Long Term Memory?
224 Citations1975Graham V. Goddard, Robert M. Douglas
The kindling effect is a relatively permanent alteration in brain function which results from repeated electrical or chemical stimulation and culminates in the appearance of electrographic and behavioral convulsions whenever the original stimulus is reapplied.
Acta Physiologica ScandinavicaExcitatory Synapses on Hippocampal Apical Dendrites Activated by Entorhinal Stimulation
210 Citations1966P. Andersen, B. Holmqvist +1 more
The results indicate that synapses located to the dendrites can initiate a local spike that may be conducted towards the soma with a low conduction velocity, and probably, with aLow safety factor.
Electroencephalography and Clinical NeurophysiologyTransfer, interference and spontaneous recovery of convulsions kindled from the rat amygdala
207 Citations1973Dan McIntyre, Graham V. Goddard
Together, the results imply that kindling establishes a lasting trace which is both transynaptic and widespread, kindling from a second location establishes a second trace utilizing parts of the existing trace, a series of convulsions leaves a less durable after-effect with a decay time of about 2 weeks and which interferes with various aspects of seizure activity, and the trace which activates the convulsion is less susceptible to interference from the after- effect.
Journal of NeurophysiologyAbnormal neuronal excitability in hippocampal slices from kindled rats
203 Citations1985Gregory L. King, Raymond Dingledine +2 more
It is concluded that either synapses or neurons intrinsic to the hippocampus are altered by kindling stimuli applied outside this brain area and the transient increase in inhibition in the dentate gyrus suggests that it may reflect a compensatory reaction to kindled seizures.
Brain ResearchRole of forebrain catecholamines in amygdaloid kindling
188 Citations1980Michael E. Corcoran, Stephen T. Mason
The results are consistent with previous evidence that noradrenaline reduces the susceptibility of the central nervous system to epileptiform activity, and they suggest that a lessening of seizure-suppressantnoradrenergic function in the forebrain might be part of the mechanism underlying kindling.
PubMedThe kindling model of epilepsy: a critical review.
185 Citations1985James O McNamara, Douglas W. Bonhaus +4 more
The kindling phenomenon is described and current understanding of the underlying mechanisms are critically reviewed to critically review whether this model of epilepsy accurately reflects analogous processes in humans.
Electroencephalography and Clinical NeurophysiologyRates of motor seizure development in rats subjected to electrical brain stimulation: strain and inter-stimulation interval effects
180 Citations1973Ronald J. Racine, W. McIntyre Burnham +2 more
Wistar rats required a significantly greater number of stimulations to develop motor seizures than did Sprague-Dawley or RVH-hooded rats and a second experiment indicated that the retardation of seizure development at short inter-stimulation intervals involved a blockade of the neural changes underlying seizure development.
Brain ResearchEffects of muscimol and picrotoxin on single unit activity of substantia nigra neurons
164 Citations1980Barbara L. Waszczak, Nancy Eng +1 more
It is suggested that a population of neurons in the substantia nigra pars reticulata have the capacity to be more affected by a major GABA input to the nigra than the pars compacta dopamine neurons, which are regulated by GABAergic neurons of the striatonigral pathway.
Experimental NeurologyElectrode placement and kindling-induced experiemental epilepsy
139 Citations1978John P. J. Pinel, Louis I. Rovner
Although the development of spontaneous interictal discharges at the stimulation site preceded the initial manifestation of spontaneous motor seizures in all rats kindled by amygdaloid or hippocampal stimulation and in a few of the animals kindled through entorhinal electrodes, such discharges were not recorded in the caudate subjects.
Journal of NeurophysiologyCellular and synaptic properties of amygdala-kindled pyriform cortex in vitro
135 Citations1986Dan McIntyre, Robert K. S. Wong
The facilitatory action of isoproterenol on spontaneous and evoked responses suggests that NE may also exert an excitatory effect and Norepinephrine and clonidine block the burst response by suppressing the underlying synaptic events.
NeurologySpontaneous recurrent seizure state induced by daily electric amygdaloid stimulation in Senegalese baboons ( <i>Papio papio</i> )
131 Citations1976Jun Wada, Takeshi Osawa
Senegalese baboons (Papio papio) represents a unique model of human epilepsy with its secondary generalized convulsive seizure development, spontaneously recurrent partial and primary generalized seizures in the background of predisposed epileptogenic susceptibility.
Experimental Brain ResearchAlterations of inhibitory processes in the dentate gyrus following kindling-induced epilepsy
124 Citations1985Michael W. Oliver, James J. Miller
Enhancement of the late Cl--insensitive inhibition was observed following the establishment of commissural kindling and persisted for periods of up to eight weeks following the last seizure.
Pharmacology Biochemistry and BehaviorThe pharmacology of seizures induced by sensitization with low intensity brain stimulation
124 Citations1973R. Babington, P. Wedeking
The low-intensity brain stimulation (LIBS) procedure has proved to be not only an interesting phenomenon, but one that responds differentially to various classes of CNS drugs.
Brain Research BulletinThe output organization of the substantia nigra in primate as revealed by a retrograde double labeling method
118 Citations1983André Parent, Ariane Mackey +2 more
The findings reveal that the SNr neurons in primate, as those in rat and cat, display a high degree of axonal branching and the output organization of SNr appears to differ markedly from that of the substantia nigra pars compacta, but is remarkably similar to the internal pallidum which is the other major output structure of the basal ganglia.
Annals of NeurologyIntradentate colchicine retards the development of amygdala kindling
114 Citations1982Richard M. Dasheiff, James O McNamara
It is concluded that DGC play a key role in the development, but not the permanence, of amygdala kindling and a model whereby the greater the input to the hippocampal formation, the faster limbic kindling will proceed is proposed.
Journal of NeurophysiologyQuantitative analysis of synaptic potentiation during kindling of the perforant path
113 Citations1986Thomas P. Sutula, Oswald Steward
Evaluation of the input-output relationships for the group of kindled animals at the various stages of evoked behavioral seizure activity revealed that increases in the population EPSP continued to slowly evolve with repeated stimulations but that increasesin the population spike were maximal after one or at most a few stimulations that evoked AD.
Journal of NeuroscienceActivation of substantia nigra neurons: role in the propagation of seizures in kindled rats
90 Citations1986DW Bonhaus, Julian R.F. Walters +1 more
The correlation between seizure-suppressant effects of lesions and SN activation during seizures leads us to propose that one mechanism by which the SN promotes seizure propagation involves SN activation and transmission of seizure activity to targets of SN.
Experimental Brain ResearchHippocampal slices of kindled rats reveal calcium involvement in epileptogenesis
88 Citations1985Wytse J. Wadman, Uwe Heinemann +2 more
A marked enhancement in extracellular calcium changes, induced by electrical stimulation or by iontophoresis of excitatory aminoacids was found in kindled tissue, implying that changes in dendritic calcium conductances are involved in kindling epileptogenesis.
Journal of NeuroscienceKnife cuts of entorhinal cortex: effects on development of amygdaloid kindling and seizure-induced decrease of muscarinic cholinergic receptors
83 Citations1985DD Savage, LC Rigsbee +1 more
The hippocampal formation circuitry facilitates the development of amygdaloid kindling and the decline of muscarinic receptors after kindled seizures is due to excessive activation of granule cells by axons from entorhinal cortex, a noncholinergic afferent.
Experimental NeurologyBehavioral analysis of amygdaloid kindling in beagle dogs and the effects of clonazepam, diazepam, phenobarbital, diphenylhydantoin, and flunarizine on seizure manifestation
79 Citations1979A. Wauquier, David Ashton +1 more
The behavioral changes seen in beagle dogs during kindling and reports on the effects of clonazepam, diazepam, phenobarbital, diphenylhy-dantoin, and flunarizine on kindled seizures are described.
Experimental NeurologySprouting fibers gain access to circuitry transsynaptically altered by kindling
78 Citations1979John A. Messenheimer, Eric W. Harris +1 more
In intact rats, “kindling” stimulation of the entorhinal cortex (EC) resulted, after an average of 23 daily stimulations, in the appearance of generalized convulsions, consistent with the hypothesis that EC kindling results in transsynaptic alterations either in the immediate targets of the EC or further “downstream” synaptically, and that destruction of the primary site of kindling causes the sprouting of projections which gain access to the altered circuitry.
Brain ResearchChemical kindling by muscarinic amygdaloid stimulation in the rat
74 Citations1983Claude G. Wasterlain, Viliam Jonec
Results demonstrate that in this model the stimulation of a group of muscarinic cholinergic synapses is both necessary and sufficient to induce a kindled state characterized by both evoked and spontaneous seizures, and support the view that epilepsy can be acquired and expressed transsynaptically.
Pharmacology Biochemistry and BehaviorEffects of γ-acetylenic GABA and γ-vinyl GABA on metrazol-activated, and kindled seizures
69 Citations1979M. Myslobodsky, Robert F. Ackermann +1 more
In rats with epilepsy kindled by amygdaloid stimulation, a single dose of GVG and five subsequent daily administrations of GAG tended to reduce the motor manifestations of seizures leaving unaffected their electrographic pattern.
Experimental NeurologyEvidence implicating dentate granule cells in development of entorhinal kindling
68 Citations1986Donald P. Frush, J.L. Giacchino +1 more
It is proposed that elimination of granule cells reduces activation of CA2/3 neurons, thereby impairing development of entorhinal kindling, in the animal model of epilepsy.
NeuropharmacologyA pharmacological study in the kindling model of epilepsy
66 Citations1984Timothy E. Albertson, R. M. Joy +1 more
The present study provides a comprehensive evaluation of carbamazepine in this model of epilepsy and discusses the results with regard to the finding reported previously.
Experimental NeurologyDepletion of noradrenaline fails to affect kindled seizures
63 Citations1984Verner S. Westerberg, Johnnye Lewis +1 more
Convulsive seizures were kindled in rats by repeated stimulation of the amygdala, and the subjects then received intracerebral injections of 6-hydroxydopamine into the dorsal noradrenergic bundle, and there was no effect on the intensity or duration of seizures.
Behavioral BiologyElectrically induced seizure activity in the hippocampus: Time course for postseizure inhibition of subsequent kindled seizures
59 Citations1978Robert S. Sainsbury, Brian H. Bland +1 more
The inhibitory effects of antecedent motor seizures produced by stimulation of the CA1 region of the dorsal hippocampus on subsequent seizure activity was investigated in kindled rats and appears to be due to the cumulative effects of a series of antecesent stimulations.
Behavioral BiologyKindling rates in inbred mice: an analog to learning?
56 Citations1976Curtis K. Leech, Dan McIntyre
The present study was undertaken to determine whether inbred mice would develop kindled convulsions in a manner similar to the manner in which they acquire an avoidance task.
Brain ResearchAspartate-induced changes in extracellular free calcium in ‘in vitro’ hippocampal slices of rats
51 Citations1982Maria Grazia Marciani, J. Louvel +1 more
Findings suggest that the decreases in [Ca2+]0 are mainly due to a postsynaptic Ca2+ entry through selective Ca2-selective conductances in rat hippocampal slices.
Electroencephalography and Clinical NeurophysiologyKindling in the frog: Development of spontaneous epileptiform activity
49 Citations1976Frank Morrell, Noriko Tsuru
The waveshape of the spontaneous epileptiform potentials exhibited an extraordinary constancy from complex to complex which was specific to each animal, which implies a constancy to both the anatomical substrate and the sequency of synaptic engagement each time spontaneous paroxysmal activity invades the network.
Experimental NeurologyKindling with low-frequency stimulation: Generality, transfer, and recruiting effects
43 Citations1981Donald P. Cain, Michael E. Corcoran
It is suggested that low-frequency stimulation is more effective than high- frequency stimulation in inducing seizure development in a variety of forebrain sites.
Experimental NeurologyDevelopment and reduction of synaptic potentiation induced by perforant path kindling
35 Citations1982Eiichi Maru, Jiro Tatsuno +2 more
Results indicate that an abnormal hyperexcitability of the granule cell was produced by the kindling stimulations, and the polysynaptic potential presumably produced through the recurrent excitatory hippocampal-entorhinal circuit was observed to increase after kindling.
Brain ResearchKindling antagonism: Interactions of dorsal and ventral entorhinal cortex with the septum during concurrent kindling
21 Citations1982James L. Burchfiel, Kevin A. Serpa +1 more
The hippocampus can be kindled via activation of its major afferents from the septum or EC, and the degree of overlap of the terminal fields of these afferentials during alternate stimulation determines their pattern of interaction.
Brain ResearchMuscarinic cholinergic regulation of epileptic spiking in kindling
18 Citations1979J. Gregory Fitz, James O McNamara
The results of these pharmacologic studies indicate that the interaction of endogenous ACh with central muscarinic receptors is capable of suppressing SIS in kindled rats, whether cholinergic suppression of SIS represents a convulsant or an anticonvulsant action is presently unclear.