Discharges In Rats Research Articles

FREQUENCY SYNCHRONIZATION REVEALS THAT SPIKE-WAVE DISCHARGES IN WAG/RIJ RATS ARE SIGNIFICANTLY NONLINEAR PHENOMENON

In this work, we studied the time-frequency dynamics of spike-wave discharges in rats with predisposition to absence epilepsy (WAG/Rij line) in two frequency ranges: 7–12,Hz and 14–24,Hz. The first and the second harmonics of the seizure main frequency lie in these ranges. Recordings of brain local field potentials of eight animals in eleven experiments of eight hour duration were analyzed. The method was based on the fast Fourier transform with a Hann’s window, and skeletons were constructed based on the obtained spectrograms. Using the skeletons, a visual and automated numerical assessment of the main frequency evolution was performed. As a result of this analysis, it was shown that temporal dynamics of the main frequency in the range 14–24,Hz follows the dynamics of the main frequency in the range 7–12,Hz. Since during the baseline activity the main frequencies in two considered ranges were developing independently, our finding indicates that the discharge is a significantly nonlinear process.

Posttraumatic and Idiopathic Spike-Wave Discharges in Rats: Discrimination by Morphology and Thalamus Involvement.

The possibility of epileptiform activity generation by the thalamocortical neuronal network after focal brain injuries, including traumatic brain injury (TBI), is actively debated. Presumably, posttraumatic spike-wave discharges (SWDs) involve a cortico-thalamocortical neuronal network. Differentiation of posttraumatic and idiopathic (i.e., spontaneously generated) SWDs is imperative for understanding posttraumatic epileptogenic mechanisms. Experiments were performed on male Sprague-Dawley rats with electrodes implanted into the somatosensory cortex and the thalamic ventral posterolateral nucleus. Local field potentials were recorded for 7 days before and 7 days after TBI (lateral fluid percussion injury, 2.5 atm). The morphology of 365 SWDs (89 idiopathic before craniotomy, and 262 posttraumatic that appeared only after TBI) and their appearance in the thalamus were analyzed. The occurrence of SWDs in the thalamus determined their spike-wave form and bilateral lateralization in the neocortex. Posttraumatic discharges were characterized by more "mature" characteristics as compared to spontaneously generated discharges: higher proportions of bilateral spreading, well-defined spike-wave form, and thalamus involvement. Based on SWD parameters, the etiology could be established with an accuracy of 75% (AUC 0.79). Our results support the hypothesis that the formation of posttraumatic SWDs involves a cortico-thalamocortical neuronal network. The results form a basis for further research of mechanisms associated with posttraumatic epileptiform activity and epileptogenesis.

Electroencephalographic investigation of the effects of Ginkgo biloba on spike-wave discharges in rats with genetic absence epilepsy

ObjectiveEGb 761, a plant extract obtained from the leaves of the Ginkgo biloba tree, is widely used in modern medicine and traditional medicine applications in the treatment of many diseases. However, in some clinical case reports, it has been suggested that G. biloba causes epileptic seizures. A limited number of experimental animal studies related to the effects of G. biloba on epileptic seizures do not provide sufficient information on the solution of a serious clinical problem with contrasting findings. We aimed to investigate the effects of EGb 761 administered in different doses to adult male Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats which is the genetic animal model of absence epilepsy, on absence seizures using in vivo electrophysiological method. In addition, the effects of EGb 761 doses on locomotor behavior of WAG/Rij rats were evaluated with open-field and rotarod behavioral tests. Methods50, 100, 200, and 400 mg/kg doses of EGb 761 were administered to male WAG/Rij rats with implanted EEG electrodes by oral gavage for 28 days. Evaluation of absence seizures was performed on spike-wave discharges (SWDs) in EEG recorded for 4 h each week. The number of SWDs, the total duration of SWDs, and the mean duration of SWD were determined for the analysis. ResultsIn the group treated with 400 mg/kg EGb 761, the number of SWDs and the mean duration of SWD at the 1st and 7th doses and the total duration of SWDs at the 1st, 7th and 14th doses were significantly increased (p < 0.05). In all experimental groups treated with EGb 761 doses, there was no significant change in locomotor activity in the open-field and the rotarod tests. ConclusionGinkgo biloba extract EGb 761 increased the epileptic SWD parameters of WAG/Rij rats at high doses (400 mg/kg), causing a pro-epileptic effect on absence seizures. It should be noted that in patients with epilepsy and in high-dose applications, G. biloba extract EGb 761 may lead to an increase in neuronal excitability.

Repetitive transcranial photobiomodulation but not long-term omega-3 intake reduces epileptiform discharges in rats with stroke-induced epilepsy.

Epilepsy is a yet under-recognized consequence after a stroke and nearly 30% of cases are pharmacoresistant. There is an unmet need for therapeutic interventions during epileptogenesis for better long-term disease outcomes. Transcranial photobiomodulation (PBM) and omega-3 (Ω-3) dietary supplementation are two approaches that have been shown promising neuroprotective effects after brain injuries. Here, we studied the PBM treatment or Ω-3 diet during epileptogenesis in long-term recurrent spontaneous abnormal electrical discharges after stroke. Wistar rats received repetitive 780 nm-laser in the scalp or oral diet with Ω-3 for 2-months after photothrombotic stroke. EEG recordings were performed 60 days after treatment end. PBM but not Ω-3 reduced both electrographic seizure duration and spikes number in the ipsilateral and contralateral cortices and ventral posteromedial thalamic nucleus. Conclusively, PBM reduced epileptiform discharges in stroke-induced epilepsy. Our results suggest the PBM as a therapeutic approach for stroke-induced epileptogenesis to minimize long-term disease outcomes.

Temporally irregular electrical stimulation to the epileptogenic focus delays epileptogenesis in rats

BackgroundVariation in the temporal patterns of electrical pulses in stimulation trains has opened a new field of opportunity for the treatment of neurological disorders, such as pharmacoresistant temporal lobe epilepsy. Whether this novel type of stimulation affects epileptogenesis remains to be investigated. ObjectiveThe purpose of this study was to analyze the effects of temporally irregular deep brain stimulation on kindling-induced epileptogenesis in rats. MethodsTemporally irregular deep brain stimulation was delivered at different times with respect to the kindling stimulation. Behavioral and electrographic changes on kindling acquisition were compared with a control group and a temporally regular deep brain stimulation-treated group. The propagation of epileptiform activity was analyzed with wavelet cross-correlation analysis, and interictal epileptiform discharge ratios were obtained. ResultsTemporally irregular deep brain stimulation delivered in the epileptogenic focus during the interictal period shortened the daily afterdischarge duration, slowed the progression of seizure stages, diminished the generalized seizure duration and interfered with the propagation of epileptiform activity from the seizure onset zone to the ipsi- and contralateral motor cortex. We also found a negative correlation between seizure severity and interictal epileptiform discharges in rats stimulated with temporally irregular deep brain stimulation. ConclusionThese results provide evidence that temporally irregular deep brain stimulation interferes with the establishment of epilepsy by delaying epileptogenesis by almost twice as long in kindling animals. Thus, temporally irregular deep brain stimulation could be a preventive approach against epilepsy.

Species-specific susceptibility to cannabis-induced convulsions.

Background and PurposeNumerous claims are made for cannabis' therapeutic utility upon human seizures, but concerns persist about risks. A potential confounder is the presence of both Δ9‐tetrahydrocannabinol (THC), variously reported to be pro‐ and anticonvulsant, and cannabidiol (CBD), widely confirmed as anticonvulsant. Therefore, we investigated effects of prolonged exposure to different THC/CBD cannabis extracts on seizure activity and associated measures of endocannabinoid (eCB) system signalling.Experimental ApproachCannabis extract effects on in vivo neurological and behavioural responses, and on bioanalyte levels, were measured in rats and dogs. Extract effects on seizure activity were measured using electroencephalography telemetry in rats. eCB signalling was also investigated using radioligand binding in cannabis extract‐treated rats and treatment‐naïve rat, mouse, chicken, dog and human tissue.Key ResultsProlonged exposure to cannabis extracts caused spontaneous, generalized seizures, subserved by epileptiform discharges in rats, but not dogs, and produced higher THC, but lower 11‐hydroxy‐THC (11‐OH‐THC) and CBD, plasma concentrations in rats versus dogs. In the same rats, prolonged exposure to cannabis also impaired cannabinoid type 1 receptor (CB1 receptor)‐mediated signalling. Profiling CB1 receptor expression, basal activity, extent of activation and sensitivity to THC suggested interspecies differences in eCB signalling, being more pronounced in a species that exhibited cannabis extract‐induced seizures (rat) than one that did not (dog).Conclusions and ImplicationsSustained cannabis extract treatment caused differential seizure, behavioural and bioanalyte levels between rats and dogs. Supporting radioligand binding data suggest species differences in eCB signalling. Interspecies variations may have important implications for predicting cannabis‐induced convulsions from animal models.Linked ArticlesThis article is part of a themed section on 8th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc

08-Development of cortical evoked potentials and epileptic after discharges in rats

Cortical interhemispheric responses in rats may serve as an index of maturation. The first two waves monosynaptically elicited by callosal fibres can be reliably evoked since the postnatal day (PD) five. The latency and duration of these evoked potentials markedly shorten after PD7. Paired-pulse stimulations demonstrate fatiguability of immature cortex; potentiation of the second response takes place since the third week. Frequency potentiation appears in the fourth postnatal week. Epileptic afterdischarges (ADs) can be elicited by low-frequency rhythmic stimulation since PD9. Their duration is longest at PD12, then it shortens. If stimulation is repeated, adult animals exhibit postictal refractoriness, i.e. an inability to elicit the second AD. This refractoriness lasting up to 3 min appeared in the fourth postnatal week, animals at PD12 and 15 exhibit marked postictal potentiation – the second, testing AD is significantly longer than the first conditioning AD. The results demonstrate that electrical stimulation induces a purely cortical phenomenon (interhemispheric responses) earlier than the complex cortico-thalamo-cortical epileptic AD. Paired stimulations demonstrate that potentiation appeared earlier in epileptic ADs than in more simple cortical evoked potentials. This study was supported by US-Czech collaborative grants No. LH11015 and LH15032 and a project of Czech Academy of Sciences No. RVO 67985823.

Why Are Children With Epileptic Encephalopathies Encephalopathic?

The epileptic encephalopathies are devastating conditions characterized by frequent seizures, severely abnormal electroencephalograms (EEGs), and cognitive slowing or regression. The cognitive impairment in the epileptic encephalopathies may be more concerning to the patient and parents than the epilepsy itself. There is increasing recognition that the cognitive comorbidity can be both chronic, primarily due to the underlying etiology of the epilepsy, and dynamic or evolving because of recurrent seizures, interictal spikes, and antiepileptic drugs. Much of scholars' understanding of the neurophysiological underpinnings of cognitive dysfunction in the epileptic encephalopathies comes from rodent studies. Frequent seizures and interictal EEG discharges in rats lead to considerable spatial and social-cognitive deficits. Paralleling these cognitive deficits are dyscoordination of dynamic neural activity within and between the neural networks that subserve normal cognitive processes.

Myocardium tissue changes caused by electrical transthoracic discharges in rats

BackgroundCardiomyocytes cytoarchitecture changes caused by transthoracic countershocks have been focused recently. We aimed to evaluate the effects of electrical discharge application in the mitochondria structure in atrial myocardium of rats.MethodsAn electrical cardioverter was adapted to small rodent animals for our research. Electrical discharges were applied to the precordial region of 30 albino rats: (1) control group - animals that remained on resting period and were afterwards sacrificed; (2) electrical discharge group - animals that remained on resting period, followed by ten electrical discharges of 300 mV and sacrificed, and; (3) electrical post-discharge group - animals that remained on a resting period and received ten electrical discharges like the electrical discharge group, but were sacrificed seven days subsequently. We examined liver, adrenal and left atrium tissue fragments of the three groups.ResultsIt was observed in control and post-discharge groups a normal cellular structure aspect with preserved architecture of cardiomyocytes and continuous sarcoplasmic membrane integrity. On the other hand, cardiac muscle fibers with mitochondrial edema and lysis occurred in the discharge group. Glycogen and adrenal lipids were not depleted in all groups.ConclusionThese data suggest that transthoracic electrical discharges induce mitochondrial injuries in atrial cardiac cells of rats.

The influence of cervical spinal cord stimulation on induced epileptic discharges in rats

Spinal cord stimulation (SCS), also known as dorsal column stimulation, is a novel technique used widely in pain surgery. However, its effect on other pathologies such as epileptic disorders is unknown. The aim of this study is to evaluate the influence of electrical epidural stimulation of the upper cervical region on epileptic cortical discharges. The long term goal is to elucidate and evaluate a therapeutic central nervous system (CNS) electrical stimulation methodology to treat epilepsy. Twelve Wistar female rats were randomly divided into two groups. In group 1 (six rats under general anesthesia), C2–3 laminectomies were performed and epidural electrodes were placed to perform SCS. To induce epileptic discharges, 1 ml (200 IU) penicillin G was microinjected into the left somatomotor cortex via left stereotactic parietal craniotomies, 0.01 to 0.1 mA at 2 Hz was used to stimulate the spinal cord. In group 2 (the control group, six rats under general anesthesia), C2–3 laminectomies were performed without electrode placement and epileptic discharges were induced with penicillin G microinjections, as described above. Both groups were monitored with digital electroencencephalography (EEG) for 70 min in seven stages and recordings analyzed with power spectral analysis. Spinal cord stimulation decreased penicillin-induced median values of epileptic discharges. Epileptic wave frequencies decreased significantly with increasing intensities of SCS. The results of this study suggest that SCS used for drug resistant epilepsies may be a viable alternative treatment modal.

7-12 Hz High-Voltage Rhythmic Spike Discharges in Rats Evaluated by Antiepileptic Drugs and Flicker Stimulation

Paroxysmal 7- to 12-Hz high-voltage rhythmic spike (HVRS) or spike-wave discharges often appear in several particular strains of rats. However, functional hypotheses of these 7-12 Hz high-voltage cortical oscillations (absence seizure vs. idling mu rhythm) are inconclusive. The mu rhythm can be provoked by flicker stimulation (FS) in most people, but FS is less effective at eliciting absence epileptic activity. Therefore FS and antiepileptic drugs were used to verify the role of HVRS activity in Long-Evans rats with spontaneous HVRS discharges and Wistar rats without spontaneous HVRS discharges. The occurrence of HVRS discharges was significantly reduced by antiabsence drugs (ethosuximide, valproic acid, and diazepam) in dose-dependent manners, but high-dose carbamazepine displayed little effect. On the other hand, oscillation frequencies and durations of spontaneous HVRS discharges were not altered by FS. Under asynchronous brain activity, many FSs (>60%) elicited small-amplitude mu-rhythm-like activity in the barrel cortex concomitant with FS-related rhythms in the occipital cortex and resulted in significant augmentation of 7-12 Hz power in the parietal region. Furthermore, a large portion of FSs (>60%) revealed increase of 7-12 Hz power of the parietal cortex after ethosuximide administration (100 mg/kg ip) in Long-Evans rats. Similar FS-elicited phenomena also appeared in Wistar rats. Characteristics of FS-elicited mu-rhythm-like activities were consistent with those observed in humans, and they remarkably differed from those of spontaneous HVRS discharges. These results support the hypothesis that HVRS activity in Long-Evans rats may be an absence-like seizure activity rather than the mu rhythm.

Audiogenic seizures associated with a cortical spreading depression wave suppress spike-wave discharges in rats

To study the role of the cortex and sub-cortical structures in the generation of epileptic spike-wave discharges in more detail, cortical and striatal activity was eliminated by the induction of spreading depression in a non-invasive way. EEG and DC potentials were recorded from the cortex and striatum of WAG/Rij rats. Several of these rats show two forms of generalised epilepsy: spontaneously occurring non-convulsive absence seizures, together with convulsive audiogenic seizures. The latter can be evoked by a brief sound stimulation, provoking a fit of wild running, which is regarded as the first phase of an audiogenic seizure. In a majority of fits the cortical DC potential does not show main changes, while the spontaneously occurring spike-wave discharges are briefly suppressed for some minutes. In a minority of fits, however, audiogenic seizures are associated with a spreading depression wave, clearly expressed in the cortical DC potential. This wave is bilaterally initiated in the cortex and propagates to the caudate nucleus of the striatum. In these cases spontaneously occurring spike-wave discharges are fully suppressed for about 1 h. It is suggested that cortical spreading depression, triggered by a short audiogenic seizure, induces a long-lasting suppression of spike-wave discharges. These results are in line with the concept that spike-wave discharges are originally initiated in the cortex, as proposed by the ‘cortical focus’ theory. The precise role of the striatum remains less clear, although this structure seems not to play a pivotal role in spike-wave generation.

Relation Between Activities of the Cortex and Vibrissae Muscles During High-Voltage Rhythmic Spike Discharges in Rats

Paroxysmal 5- to 12-Hz high-voltage rhythmic spike (HVRS) activities, which are accompanied by whisker twitching (WT), are found in Long Evans rats, but the function of these HVRS activities is still debated. In four major functional hypotheses of HVRS discharges, i.e., alpha tremor, attention/mu rhythm, idling/mu rhythm, and absence seizure, the first two hypotheses emphasize WT behavior in HVRS bouts. Whisker movement is primarily determined by activation of intrinsic and extrinsic muscles. To clarify the role of WT in HVRS activities, simultaneous recording of the activities from the cortex and intrinsic/extrinsic and neck muscles were performed. Most HVRS bouts (68.8%) revealed no time-locked WT behavior in a 2-h recording session. In addition, WT primarily arose from active protraction due to activation of intrinsic muscles followed by passive retraction. A small portion of WT resulted from activation of both vibrissae muscles with dynamic frequency-dependent phase shifts. Onset of the rhythmic vibrissae EMG significantly lagged behind HVRS onset, and the mean duration of vibrissae muscle activity was one-third to a one-half of a HVRS bout. Moreover, a greater number of HVRS bouts were associated with a longer HVRS duration and higher oscillation frequency. Oscillation frequencies of HVRS activities without WT behavior were significantly lower than those with WT. Under peripheral sensory/motor blockade by xylocaine injection, oscillation frequencies of HVRS bouts significantly decreased, but no remarkable changes in the number or duration of HVRS bouts were observed. Compared with vibrissa muscle activity during WT and exploratory whisking, the duration of muscular activity in each cycle was apparently longer during whisking bouts. Based on these results, overemphasis of the role of WT on HVRS activities might not be appropriate. Instead, HVRS discharges may be associated with absence seizure or idling state. In addition, peripheral inputs, including WT, may elevate the oscillation frequency of HVRS bouts. Moreover, different muscular controls may exist between WT and whisking.

Alteration of the second branch of the trigeminal nerve activity following inferior alveolar nerve transection in rats

After transection of the inferior alveolar nerve (IAN), the whisker pad area, which is innervated by the infraorbital nerve (ION) that was not injured, showed hypersensitivity to mechanical stimulation. Two days after IAN transection, threshold intensity for escape behavior to mechanical stimulation of the ipsilateral whisker pad area was less than 4.0 g, indicating mechanical allodynia. A total of 68 single fiber discharges were recorded from ION fibers at 3 days after IAN transection. The responses of C- and A-fibers were classified according to their conduction velocity. The C-fiber activities were not affected by IAN transection, whereas A-fiber activities were significantly enhanced by IAN transection as indicated by an increase in background activity and mechanically evoked response. Since the A-fiber responses were significantly affected by IAN transection, patch clamp recording was performed from middle to large diameter retrogradely labeled and acutely dissociated trigeminal ganglion (TRG) neurons. The I K (sustained) and I A (transient) currents were significantly smaller and hyperpolarization-activated current ( I h) was significantly larger in TRG neurons of rats with IAN transection as compared to those of naive rats. Furthermore, current injection into TRG neurons induced high frequency spike discharges in rats with IAN transection. These data suggest that changes in K + current and I h observed in the uninjured TRG neurons reflect an increase in excitability of TRG neurons innervated by the ION after IAN transection, resulting in the development of mechano-allodynia in the area adjacent to the injured IAN innervated region.

Activation of peripheral NMDA receptors contributes to human pain and rat afferent discharges evoked by injection of glutamate into the masseter muscle.

Peripheral N-methyl-d-aspartate (NMDA) receptors are found in deep tissues and may play a role in deep tissue pain. Injection of the endogenous NMDA receptor agonist glutamate into the masseter muscle excites deep craniofacial afferent fibers in rats and evokes pain in human subjects. It is not clear whether peripheral NMDA receptors play a role in these effects of glutamate. Accordingly, the effect of NMDA on afferent activity as well as the effect of locally administered NMDA receptor antagonists on glutamate-evoked afferent discharges in acutely anesthetized rats and muscle pain in human subjects was examined. Injection of NMDA into the masseter muscle evoked afferent discharges in a concentration-related manner. It was found that the NMDA receptor antagonists 2-amino-5-phosphonvalerate (APV, 10 mM), ketamine (10 mM), and dextromethorphan (40 mM) significantly decreased glutamate-evoked afferent discharges. The effects of APV and ketamine, but not dextromethorphan, were selective for glutamate-evoked afferent discharges and did not affect hypertonic saline-evoked afferent discharges. In human experiments, it was found that 10 mM ketamine decreased glutamate-evoked muscle pain but had no effect on hypertonic saline-evoked muscle pain. These results indicate that injection of glutamate into the masseter muscle evokes afferent discharges in rats and muscle pain in humans in part through activation of peripheral NMDA receptors. It is conceivable that activation of peripheral NMDA receptors may contribute to masticatory muscle pain and that peripherally acting NMDA receptor antagonists could prove to be effective analgesics for this type of pain.

Sialic acid contributes to generation of ectopic spontaneous discharges in rats with neuropathic pain

Ectopic spontaneous discharges (ESD) of teased myelinated fibers were recorded from the sciatic nerve proximal to the site of ‘chronic constriction nerve injury’ in the rat. Ca 2+, Mg 2+, Mn 2+, Ni 2+, La 3+ and some positively charged organic compounds (hexamethonium and poly-lysine) when applied topically to the injured site abolished or significantly reduced the rate of ESD. After enzymatic removal of sialic acid by neuraminidase (2 units/ml), the ESD was silenced in 11, reduced in four and unchanged in four of 19 fibers. However, divalent cations failed to depress the reappeared ESD evoked by 4-aminopyridine in the desialylated silenced fibers. Moreover, the mean incidence of ESD was significantly reduced after neuraminidase treatment. These results indicate that an increase in negative charges on the external membrane surface of injured neuron caused by sialylation is a key factor in ESD generation.

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. Next, the stimuli were presented in the test phase in pseudorandom order during spike-wave discharges. The reactivity of the ongoing EEG was analysed. It was found that the presentation of the reinforced stimulus induced a larger number of aborted spike-wave discharges than the non-reinforced stimulus, regardless of the intensity of the stimuli. This implies that during generalised spike-wave discharges the brain is still capable of evaluating the meaning of an ictally presented stimulus. It also shows that sensory, attentional and mnemonic processes are at least partially intact during the occurrence of a spike-wave discharge. The results of the present study are largely in agreement with results on human spike-wave activity-related cognitive disturbances. Moreover, they may lead to a refinement of the concept of epileptic consciousness and may emphasise the heuristic value of rodent models for studying both ictal and interictal information processing.

Intracellular recordings in thalamic neurones during spontaneous spike and wave discharges in rats with absence epilepsy.

1. In vivo extracellular and intracellular recordings were performed from thalamocortical (TC) neurones in a genetic model of absence epilepsy (genetic absence epilepsy rats from Strasbourg) during spontaneous spike and wave discharges (SWDs). 2. Extracellularly recorded single units (n = 14) fired either a single action potential or a high frequency burst of up to three action potentials, concomitantly with the spike component of the spike-wave complex. 3. Three main events characterized the intracellular activity of twenty-six out of twenty-eight TC neurones during SWDs: a small amplitude tonic hyperpolarization that was present throughout the SWD, rhythmic sequences of EPSP/IPSPs occurring concomitantly with the spike-wave complexes, and a small tonic depolarization at the end of the SWD. The rhythmic IPSPs, but not the tonic hyperpolarization, were mediated by activation of GABAA receptors since they reversed in polarity at -68 mV and appeared as depolarizing events when recording with KCl-filled electrodes. 4. The intracellular activity of the remaining two TC neurones consisted of rhythmic low threshold Ca2+ potentials, with a few EPSP/IPSP sequences present at the start of the SWD. 5. These results obtained in a well-established genetic model of absence epilepsy do not support the hypothesis that the intracellular activity of TC neurones during SWDs involves rhythmic sequences of GABAB IPSPs and low threshold Ca2+ potentials.

2117 Effects of serotonin on fluctuations in single neuronal activities in the region of the lateral geniculate nucleus of a cat

Pharmacological data have shown that the cholinergic transmission participates in the control of spike-and-wave discharges in rats with genetic absence epilepsy. The corticothalamic circuitry which generates spontaneous spike-and-wave discharges, the electroencephalographic expression of absence seizures, receives important cholinergic inputs from two distinct sources: (i) the nucleus basalis projecting mainly to the cortex and (ii) the pedunculopontine and laterodorsal tegmental nuclei providing cholinergic afferents to the thalamus. In the present study, the involvement of the cholinergic mesopontothalamic projections in the control of spike-and-wave discharges was investigated. Activation of cell bodies in the pedunculopontine and laterodorsal tegmental nuclei, by local microinjections of non-toxic doses of kainate (20 pmol/side) or picrotoxin (66 pmol/side), suppressed spike-and-wave discharges. Similar effects were produced by direct cholinergic activation of the ventrolateral part of the thalamus: intrathalamic microinjections of carbachol (0.7-2.8 pmol/side), a cholinergic receptor agonist, resulted in a dose-dependent suppression of spike-and-wave discharges. This suppression was partially reversed by a sumultaneous microinjection of an equimolar dose of scopolamine, a muscarinic receptor antagonist. Electrolytic or neuroexcitotoxic lesions of the pedunculopontine and laterodorsal tegmental nuclei did not modify spike-and-wave discharges.These results suggest that the cholinergic mesopontine projection to the thalamus exerts a phasic inhibitory control of generalized non-convulsive epileptic seizures.

Mesopontine cholinergic control over generalized non-convulsive seizures in a genetic model of absence epilepsy in the rat.

Pharmacological data have shown that the cholinergic transmission participates in the control of spike-and-wave discharges in rats with genetic absence epilepsy. The corticothalamic circuitry which generates spontaneous spike-and-wave discharges, the electroencephalographic expression of absence seizures, receives important cholinergic inputs from two distinct sources: (i) the nucleus basalis projecting mainly to the cortex and (ii) the pedunculopontine and laterodorsal tegmental nuclei providing cholinergic afferents to the thalamus. In the present study, the involvement of the cholinergic mesopontothalamic projections in the control of spike-and-wave discharges was investigated. Activation of cell bodies in the pedunculopontine and laterodorsal tegmental nuclei, by local microinjections of non-toxic doses of kainate (20 pmol/side) or picrotoxin (66 pmol/side), suppressed spike-and-wave discharges. Similar effects were produced by direct cholinergic activation of the ventrolateral part of the thalamus: intrathalamic microinjections of carbachol (0.7-2.8 pmol/side), a cholinergic receptor agonist, resulted in a dose-dependent suppression of spike-and-wave discharges. This suppression was partially reversed by a simultaneous microinjection of an equimolar dose of scopolamine, a muscarinic receptor antagonist. Electrolytic or neuroexcitotoxic lesions of the pedunculopontine and laterodorsal tegmental nuclei did not modify spike-and-wave discharges. These results suggest that the cholinergic mesopontine projection to the thalamus exerts a phasic inhibitory control of generalized non-convulsive epileptic seizures.