Pedunculopontine neurons are involved in network changes in the kindling model of temporal lobe epilepsy

It is well known that epileptogenesis is associated with widespread neuronal network changes in brain regions adjacent to the seizure focus but also in remote structures including basal ganglia. Besides the superior colliculus, the pedunculopontine tegmental nucleus (PPN) is one of three main target regions of basal ganglia output activity and is reciprocally connected with the substantia nigra pars reticulata (SNr), which is critically involved in seizure propagation and manipulation. We here tested the hypothesis if, apart from the traditional view that the superior colliculus mediates seizure-gating mechanisms of the SNr, the PPN is involved in kindling-induced network changes. Rats were electrically kindled via the ipsilateral basolateral amygdala. In vivo extracellular single unit recordings of right PPN neurons were performed in kindled rats 1 day after a generalized seizure in order to examine kindling-associated rather than seizure-associated activity changes. The main findings of the study were (1) a seizure-outlasting drastically reduced firing rate of PPN neurons and (2) an increase in burst and irregular firing pattern in kindled rats compared with sham-kindled and naïve controls. These changes are likely to be caused by an altered inhibitory input from the SNr. Furthermore, kindling caused (3) the oscillation frequency of PPN neurons to shift towards lower frequencies. The kindling-induced activity changes were found to be anatomically restricted to the PPN, indicating that network changes follow distinct anatomical routes. We demonstrated that the PPN is strongly affected by the functional reorganization of neurocircuitry associated with kindling. The underlying mechanisms are discussed. The findings are relevant for a better understanding of kindling-associated network changes and might provide new targets for therapeutic manipulations in epilepsies.