Suppression of absence seizures by electrical and pharmacological activation of the caudal superior colliculus in a genetic model of absence epilepsy in the rat.

Activation of the superior colliculus has been shown to reproduce the antiepileptic effect of the inhibition of the substantia nigra reticulata. A circuit involving neurons of the caudal deep layers of the superior colliculus has been suggested to control brain stem convulsive seizures. The present study was designed to examine whether a similar circuit is also involved in the control of absence seizures. For this, activation of either the rostral or caudal parts of the deep and intermediate layers of the superior colliculus was applied in a genetic model of absence seizures in the rat (GAERS). Single-shock (5 s) electrical stimulation of the rostral and caudal superior colliculus interrupted ongoing spike-and-wave discharges at an intensity (antiepileptic threshold) significantly lower than the intensity inducing behavioral effects. At this intensity, no interruption of licking behavior was observed in water-deprived rats. Repeated stimulations (5 s on/5 s off) at the antiepileptic threshold reduced absence seizures only during the first 10 min. Bilateral microinjection of a GABA antagonist (picrotoxin, 33 pmol/side) significantly suppressed spike-and-wave discharges when applied in the caudal aspect of the superior colliculus. This antiepileptic effect appears dissociated from an anxiogenic effect, as tested in an elevated plus maze test. Finally, bilateral injection of picrotoxin (33 pmol/side) appeared more effective in the superficial and intermediate layers of the caudal superior colliculus, whereas such injections had only weak effects on absence seizures when applied in the deep layers. These results suggest that a specific population of neurons located in the intermediate and superficial layers of the caudal superior colliculus is involved in the inhibitory control of absence seizures. It may constitute an important relay for the control of absence seizures by the basal ganglia via the substantia nigra reticulata.

Influences of the bed nucleus of the stria terminalis and of the paraventricular nucleus of the hypothalamus on the excitability of hippocampal-lateral septal synapses in mice.

Previous experiments have shown that conditioning in aversive situations is associated with specific changes in excitability of hippocampal-septal synaptic transmission and that these changes might be related to a modulation of this synaptic transmission by afferents originating from the bed nucleus of the stria terminalis (BNST) and from the paraventricular nucleus (PVN) of the hypothalamus. Accordingly, the aim of the present experiment was to assess changes in excitability of hippocampal-septal synapses by varying the interval between the application of a conditioning pulse in either the BNST or the PVN, and a test pulse in fimbria fibers (FF). Electrical stimulation of FF, induces in the lateral septum (LS) a field potential characterized by two negative waves (N2 and N3) the magnitude of which is an index of excitability of two populations of target cells located in the ventral and dorsal lateral septum, respectively. Results showed that prestimulation of both the BNST and the PVN produced an increase in the amplitude of the N3 wave, although the optimal interpulse interval required for producing maximal increase was different as a function of the two structures. Only prestimulation of the BNST induced a significant increase in the amplitude of the N2 wave. These results suggest that the PVN projects mainly to the dorsal aspect of the LS, while the BNST projects to both dorsal and ventral parts of the LS. Together with results from previous experiments conducted in behaving mice exposed to conditioned aversive stimuli, it is concluded that these projections might play a role in the relief of contextual conditioned fear.