SPIKE-WAVE COMPLEXES AND FAST COMPONENTS OF CORTICALLY GENERATED SEIZURES - IV - PAROXYSMAL FAST RUNS IN CORTICAL AND THALAMIC NEURONS

In the preceding papers of this series, we have analyzed the cellular patterns and synchronization of neocortical seizures occurring spontan eously or induced by electrical stimulation or cortical infusion of bi cuculline under a variety of experimental conditions, including natura l states of vigilance in behaving animals and acute preparations under different anesthetics. The seizures consisted of mio distinct compone nts: spike-wave (SW) or polyspike-wave (PSW) at 2-3 Hz and fast runs a t 10-15 Hz. Because the thalamus is an input source and target of cort ical neurons, we investigated here the seizure behavior of thalamic re ticular (RE) and thalamocortical (TC) neurons, two major cellular clas ses that have often been implicated in the generation of paroxysmal ep isodes. We performed single and dual simultaneous intracellular record ings, in conjunction with multisite field potential and extracellular unit recordings, from neocortical areas and RE and/or dorsal thalamic nuclei under ketamine-xylazine and barbiturate anesthesia. Both compon ents of seizures were analyzed, but emphasis was placed on the fast ru ns because of their recent investigation at the cellular level. I) The fast runs occurred at slightly different frequencies and, therefore, were asynchronous in various cortical neuronal pools. Consequently, do rsal thalamic nuclei, although receiving convergent inputs from differ ent neocortical areas involved in seizure, did not express strongly sy nchronized fast runs. 2) Both RE and TC cells were hyperpolarized duri ng seizure episodes with SW/PSW complexes and relatively depolarized d uring the fast runs. As known, hyperpolarization of thalamic neurons d einactivates a low-threshold conductance that generates hi,oh-frequenc y spike bursts. Accordingly, RE neurons discharged prolonged high-freq uency spike bursts in close time relation with the spiky component of cortical SW/PSW complexes, whereas they fired single action potentials , spike doublers, or triplets during the fast runs. In TC cells, the c ortical fast runs were reflected as excitatory postsynaptic potentials appearing after short latencies that were compatible with monosynapti c activation through corticothalamic pathways. 3) The above data sugge sted the cortical origin of these seizures. To further test this hypot hesis, we performed experiments on completely isolated cortical slabs from suprasylvian areas 5 or 7 and demonstrated that electrical stimul ation within the slab induces seizures with fast runs and SW/PSW compl exes, virtually identical to those elicited in intact-brain animals. T he conclusion of all papers in this series is that complex seizure pat terns, resembling those described at the electroencephalogram level in different forms of clinical seizures with SW/PSW complexes and, parti cularly, in the Lennox-Gastaut syndrome of humans, are generated in ne ocortex. Thalamic neurons reflect cortical events as a function of mem brane potential in RE/TC cells and degree of synchronization in cortic al neuronal networks.