Audiogenic kindling induces plastic changes in the neuronal firing patterns in periaqueductal gray

The ventrolateral periaqueductal gray (vlPAG) is a critical structure in the requisite neuronal network for audiogenic seizures (AGS), which is confined to the brainstem, in genetically epilepsy-prone rats (GEPR-9s). Periodic repetition of AGS in GEPR-9s induces AGS kindling resulting in expansion of the seizure network to the forebrain, epileptiform electrocorticographic activity, and prolonged seizure duration due to emergence of a previously unexpressed seizure behavior-generalized clonus (post-tonic clonus, PTC). The pathway that mediates AGS kindling has been shown to involve the amygdala, which is known to have extensive projections to the periaqueductal gray. The present study investigated whether AGS kindling results in changes in vlPAG neuronal firing by chronically implanting microwire electrodes to record vlPAG extracellular action potentials in awake-behaving GEPR-9s. Acoustic responses and neuronal firing patterns during AGS were compared in non-kindled and AGS kindled GEPR-9s. AGS kindling induced significant increases in acoustic responsiveness of vlPAG neurons. During AGS in both AGS kindled and non-kindled GEPR-9s, vlPAG neurons displayed tonic firing during wild running and tonic extension behaviors. However, the tonic firing pattern changed to burst firing exclusively during PTC, and this vlPAG neuronal firing change was seen only in kindled GEPR-9s. Burst firing is a hallmark of neuroplastic changes known to mediate increased synaptic efficiency. These results suggest that the amygdala to vlPAG pathway may be a critical element of the expanded seizure network that contributes importantly to the emergence of PTC induced by AGS kindling in GEPR-9s, which is supported by recent preliminary studies of this pathway.