Influence of transcranial magnetic stimulation on spike-wave discharges in a genetic model of absence epilepsy.

Transcranial magnetic stimulation (TMS) impulses, (0.5 Hz, 3 impulses) were presented at threshold intensity to male WAG/Rij rats. One group received stimuli, which involved motor responses of hindlimbs, rats of the second group received sham stimulation.

Are there different mechanisms of synchronization in the course of spike-wave discharges (SWDs) burst development in WAG/Rij rats?

In WAG/Rij rats the pair linear correlation r was calculated for bipolar recordings in fronto-temporal, fronto-occipital and occipito-temporal zones of both hemispheres as well as in paleocerebellar cortex (culmen). It was shown that development of SWD bursts resulted in interhemispheric decreases of correlation between the right occipito-temporal cortical region on one side, and left fronto-temporal on the contralateral side. Towards the end of SWD, we found an increased interhemispheric correlation between left fronto-temporal and right fronto-occipital cortical zones, as well as, between both fronto-temporal zones.

The brain 5HTergic response to an acute sound stress in rats with generalized (absence and audiogenic) epilepsy.

The brain serotoninergic (5HTergic) system of epileptic subjects can influence their vulnerability to stress. We studied the putative dependency of 5HT neurotransmission parameters on emotional stress, and the presence, types and severity of seizures using rats with genetic generalized (absence and/or audiogenic) epilepsy, of WAG/Rij and Wistar strains. The animals were stressed by exposure to a short aversive noise or left without sound stimulation.

Measuring clusters of spontaneous spike-wave discharges in absence epileptic rats.

Spike-wave discharges (SWDs) characterizing absence epilepsy appear in closely packed aggregated sequences, which gave rise to the name "pyknolepsy" for this disease. In WAG/Rij rats, genetically prone to absence epilepsy, spontaneous SWDs seem to occur in clusters as well. Here, we aimed to quantify the seizures' clusters.

The preferential mGlu2/3 receptor antagonist, LY341495, reduces the frequency of spike-wave discharges in the WAG/Rij rat model of absence epilepsy.

We examined the expression and function of group-II metabotropic glutamate (mGlu) receptors in an animal model of absence seizures using genetically epileptic WAG/Rij rats, which develop spontaneous non-convulsive seizures after 2-3 months of age. Six-month-old WAG/Rij rats showed an increased expression of mGlu2/3 receptors in the ventrolateral regions of the somatosensory cortex, ventrobasal thalamic nuclei, and hippocampus, but not in the reticular thalamic nucleus and in the corpus striatum, as assessed by immunohistochemistry and Western blotting. In contrast, mGlu2/3 receptor signalling was reduced in slices prepared from the somatosensory cortex of 6-month-old WAG/Rij rats, as assessed by the ability of the agonist, LY379268, to inhibit forskolin-stimulated cAMP formation.

The multiple effects of ketamine on electroencephalographic activity and behavior in WAG/Rij rats.

The effects of ketamine, a noncompetitive antagonist at the NMDA receptor, were studied on the EEG and in the open field in a genetic animal model of generalized absence epilepsy--the WAG/Rij rat strain. Animals of this strain display spontaneous occurring generalized spike-wave discharges (SWDs) in the EEG. Ketamine was systemically administered in a dose range from 3 to 30 mg/kg.

The effects of early maternal deprivation on auditory information processing in adult Wistar rats.

Background: There is now ample evidence that schizophrenia is due to an interaction between genetic and (early) environmental factors which disturbs normal development of the central nervous system and ultimately leads to the development of clinical symptoms. Recently, we showed that a single 24-hour period of maternal deprivation of rat pups at postnatal day 9 leads to a disturbance in prepulse inhibition, similar to what is seen in schizophrenia. The present set of experiments was designed to further characterize the information processing deficits of maternally deprived Wistar rats.

[The cortico-thalamic theory for generalised spike-wave discharges].

The origin of generalized absence epilepsy is still not known. In the last century, four theories have dominated the debate about the origin of the bilateral synchronous generalized spike-wave discharges associated with absence seizures: the "centrencephalic" theory [Penfield and Jasper], the "cortical" [Bancaud, Niedermeyer, Luders], the "cortico-reticular" theory [Gloor, Kostop[oulos, Avoli] and the "thalamic clock" theory [Buzsaki]. There is now some evidence that absence epilepsy, as studied in the WAG/Rij model, is a corticothalamic type of epilepsy.

Differential expression of high voltage-activated Ca2+ channel types in the rostral reticular thalamic nucleus of the absence epileptic WAG/Rij rat.

In the WAG/Rij rat, a model for human absence epilepsy, spike-wave discharges (SWD) and absence epileptic behavior develop after the age of 3 months. The rostral part of the reticular thalamic nucleus (rRTN) is involved in SWD. Ca(2+) channels play a central role in the initiation and maintenance of burst firing activity of thalamic cells.

Synaptology of the rostral reticular thalamic nucleus of absence epileptic WAG/Rij rats.

The adult WAG/Rij rat is a well-established animal model for human absence epilepsy characterized by the presence of spike-wave discharges (SWDs). The pacemaking activity of the rostral reticular thalamic nucleus (rRTN) has been demonstrated to be essential for SWD maintenance. We investigated if SWD maintenance can be related to the synaptic organization of the rRTN, by studying the ultrastructure of the rRTN of absence epileptic WAG/Rij rats in comparison with that of non-epileptic, age-matched ACI control rats.

Genetic animal models for absence epilepsy: a review of the WAG/Rij strain of rats.

Based on the reviewed literature and the data presented in this paper, conclusions can be drawn with respect to the validity of the WAG/Rij strain of rats as a model for absence epilepsy in humans. The view that the WAG/Rij model has "face validity" is supported by the simultaneous presence of clinical and electroencephalographic signs characterizing absences in rat and humans, by the decrease in responsiveness during the presence of spike-wave discharges in both species, by the agreement between model and patient with respect to the preferential occurrences of spike-wave discharges at transitions in states of vigilance, by the corresponding modulation of spike-wave discharges by physical and mental activities in both and, finally, by the fact that in both humans and rats absence epilepsy is inherited. Against this view, however, argue two points.

Slow late component in conditioned stimulus-evoked potentials from the amygdala after fear conditioning in the rat.

Male Wistar rats were subjected to a differential Pavlovian fear conditioning procedure in which one of two tones (6 or 10 kHz) was followed by an electric shock (CS+) and the other was not (CS-). Before and after fear conditioning, we recorded the evoked potentials elicited by CS+ and CS- from electrodes aimed at the lateral nucleus of the amygdala. Before conditioning, a slow, negative component with peak amplitude around 150 ms was present in the evoked potentials.

Ictal stimulus processing during spike-wave discharges in genetic epileptic rats.

In the present experiment it was investigated whether and to what extent auditory information processing is possible during the presence of spike-wave discharges in rats. To that end, WAG/Rij rats which are an animal model for absence epilepsy, were provided with cortical electrodes for the registration of the electroencephalogram (EEG). The animals were first trained in an appetitively motivated conditioning paradigm to learn to discriminate between two auditory stimuli with equal duration and frequency but with different intensities.

[Cholinergic mechanisms in the pathogenesis of genetically-caused absence epilepsy].

Frontoparietal cortex and the thalamocortical circuit comprising reticular thalamic nucleus (RTN) and relay nuclei of the ventrolateral thalamus (VLT) are critical structures in the generation of spike-wave discharges (SWD) during absence seizures. The activity of these nuclei is under the control of the ascending cholinergic projections of nucleus basalis of Meynert. The aim of our study is to make an attempt to change the pattern of SWD in WAG/Rij rats by injecting of cholinotoxine AF64A to the area of RTN.

Rat models of genetic absence epilepsy: what do EEG spike-wave discharges tell us about drug effects?

Electroencephalographic studies in the WAG/Rij rats of Nijmegen and genetic absence epileptic rats of Strasbourg (GAERS), two genetic models for human generalized absence epilepsy, illustrate the usefulness of drug-electroencephalogram (EEG) interaction studies. In the EEG of both types of rats, spontaneously occurring spike-wave discharges are present. For drug discovery, a model with predictive validity is imperative, and both the WAG/Rij and the GAERS models seem adequate.

[Pregnancy in WAG/Rij rats--changes in the levels of progesterone, estradiol and generalized absence epilepsy].

Progesterone and oestradiol serum level was investigated in WAG/Rij rats with genetically determined absences. Blood samples were drawn before and after the pregnancy following the parturition. The serum concentration of progesterone increased after the 3rd day of pregnancy.

Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats.

Absence seizures are the most pure form of generalized epilepsy. They are characterized in the electroencephalogram by widespread bilaterally synchronous spike-wave discharges (SWDs), which are the reflections of highly synchronized oscillations in thalamocortical networks. To reveal network mechanisms responsible for the initiation and generalization of the discharges, we studied the interrelationships between multisite cortical and thalamic field potentials recorded during spontaneous SWDs in the freely moving WAG/Rij rat, a genetic model of absence epilepsy.

Habituation and sensitization in rat auditory evoked potentials: a single-trial analysis with wavelet denoising.

In this work, systematic changes of single-trial auditory evoked potentials elicited in rats were studied. Single-trial evoked potentials were obtained with the help of wavelet denoising, a very recently proposed method that has already been shown to be useful in the analysis of scalp human evoked potentials. For the evoked components in the 13-24-ms range (i.

Dopamine characteristics in rat genotypes with distinct susceptibility to epileptic activity: apomorphine-induced stereotyped gnawing and novelty/amphetamine-induced locomotor stimulation.

Rat genotypes differ in their susceptibility to spontaneously occurring spike-wave discharges and in their dopaminergic properties. In a previous study, it was found that spike-wave discharge incidence decreased in the following order in four rat genotypes during baseline and following injection with the dopamine antagonist haloperidol: apomorphine-susceptible (APO-SUS) > WAG/Rij > apomorphine-unsusceptible (APO-UNSUS) and ACI rats. The question in the present study was to what extent certain dopaminergic properties are pathognomonic for epileptic rats.

Auditory information processing in rat genotypes with different dopaminergic properties.

Rationale: Auditory filtering disturbances, as measured in the sensory gating and prepulse inhibition (PPI) paradigms, have been linked to aberrant auditory information processing and sensory overload in schizophrenic patients. In both paradigms, the response to the second stimulus (S2) is attenuated by an inhibitory effect of the first stimulus (S1). Dopamine (DA) agonists have been found to reduce gating of auditory evoked potentials (AEPs) and PPI in healthy human subjects and in rats.

Electrophysiological and pharmacological characteristics of two types of spike-wave discharges in WAG/Rij rats.

Rats of the WAG/Rij strain are commonly seen as a genetic model for generalised absence epilepsy in man. Interestingly, generalised absence epilepsy shows, in addition to the fully generalised spike-wave discharges, a second type of spike-wave discharge, which lasts for a shorter time, has a lower frequency, and a lower incidence. The originally described distinction between the two types of spike-wave discharges was mainly based on the shape, polarity and duration of the discharges.

Hippocampal and cortical sensory gating in rats: effects of quinpirole microinjections in nucleus accumbens core and shell.

Sensory processing disturbances, as measured in the P50/sensory gating paradigm, have been linked to aberrant auditory information processing and sensory overload in schizophrenic patients. In this paradigm, the response to the second of paired-click stimuli is attenuated by an inhibitory effect of the first stimulus. Sensory gating has been observed in most healthy human subjects and normal laboratory rats.

Auditory evoked potentials from auditory cortex, medial geniculate nucleus, and inferior colliculus during sleep-wake states and spike-wave discharges in the WAG/Rij rat.

Objective: Click auditory evoked potentials (AEP) were simultaneously recorded from the auditory cortex (ACx), the medial geniculate nucleus (MGN), and the inferior colliculus (IC) in the freely moving WAG/Rij rat, to investigate state-dependent changes of the AEP in different anatomical locations along the auditory pathway.

Methods: AEPs obtained during active (AW) and passive wakefulness (PW), slow wave sleep (SWS), rapid-eye-movement sleep (REM) and generalized spike-wave discharges (SWD; a specific trait of the WAG/Rij rat, a genetic model for absence epilepsy), were compared.

Results: The early components in ACx, MGN and IC were stable throughout the sleep-wake cycle and SWD, apart from a slight increase in the IC during SWD.

PTZ-induced seizures in rats: effects of age and strain.

The susceptibility to pentylenetetrazol (PTZ)-induced seizures during postnatal ontogeny [postnatal day (PN) 10-220] was investigated in two rat strains. The WAG/Rij strain, genetically prone for developing generalized absence epilepsy, and Wistar rats were tested and compared at PN 10, 26, 30, 70, 90, 125, and 220 on the PTZ-convulsive threshold. A subconvulsive dose of 25-mg/kg PTZ was administered every 15 min, and the occurrence of clonic and tonic-clonic seizures was scored.

Sensory gating of auditory evoked potentials in rats: effects of repetitive stimulation and the interstimulus interval.

In the P50 gating or conditioning-testing (C-T) paradigm, the P50 response, a small positive midlatency ( approximately 50 ms after stimulus onset) component of the human auditory evoked potential (AEP), is reduced towards the second click (S2) as compared to the response to the first click (S1). This phenomenon is called sensory gating. The putative function of sensory gating is thought to protect subjects from being flooded by irrelevant stimuli.