: Parafascicular nucleus and control of seizures

International audiencePURPOSE: The aim of this study was to investigate whether the nucleus parafascicularis (Pf) of the thalamus could be a relay of the control of epileptic seizures by the superior colliculus (SC). The Pf is one of the main ascending projections of the SC, the disinhibition of which has been shown to suppress seizures in different animal models and has been proposed as the main relay of the nigral control of epilepsy. METHODS: Rats with genetic absence seizures (generalized absence epilepsy rat from Strasbourg or GAERS) were used in this study. The effect of bilateral microinjection of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist, in the SC on the glutamate and GABA extracellular concentration within the Pf was first investigated by using microdialysis. In a second experiment, the effect of direct activation of Pf neurons on the occurrence of absence seizures was examined with microinjection of low doses of kainate, a glutamate agonist. RESULTS: Bilateral injection of picrotoxin (33 pmol/side) in the SC suppressed spike-and-wave discharges for 20 min. This treatment resulted in an increase of glutamate but not GABA levels in the Pf during the same time course. Bilateral injection of kainate (35 pmol/side) into the Pf significantly suppressed spike-and-wave discharges for 20 min, whereas such injections were without effects when at least one site was located outside the Pf. CONCLUSIONS: These data suggest that glutamatergic projections to the Pf could be involved in the control of seizures by the SC. Disinhibition of these neurons could lead to seizure suppression and may be involved in the nigral control of epilepsy

Anatomical evidence for an anticonvulsant relay in the rat ventromedial medulla

Pharmacological manipulation of the ventrolateral pontine reticular formation (vlPRF) of rats has an anticonvulsant effect in the maximal electroshock model of epilepsy. This study presents three anatomical experiments that determine the efferent projections from this region likely to mediate this anticonvulsant effect. In the first, the anterograde tracer biotinylated dextran amine (BDA) was injected into the vlPRF. A strong projection to the ventromedial medullary reticular formation (vmMRF) was revealed which continued only weakly to the spinal cord. In the second experiment, double-label procedures were used to indicate whether the BDA-labelled terminals from the vlPRF make contacts with neurons in vmMRF, retrogradely labelled with cholera-toxin B subunit from the lumbar spinal cord. Sections of the vmMRF were examined by: (i) light microscopy which showed significant overlap between terminals from vlPRF and retrogradely-labelled reticulospinal cells; (ii) confocal microscopy which showed labelled terminals in close association with reticulospinal cell bodies; and (iii) electron microscopy which showed vlPRF terminals making synaptic contact with reticulospinal neurons. Finally, immunohistochemical procedures in combination with anterograde tracing revealed that significant numbers of terminals labelled from vlPRF were also positive for markers of glutamatergic or GABAergic neurotransmission. This suggests that the projection from the vlPRF to the vmMRF is likely to include several different functional components. These connections could represent a final critical link of an anticonvulsant circuit that originates in the dorsal midbrain and projects via relays in the vlPRF and the vmMRF to interact with the low-level motor circuitry in the spinal cord