Phenytoin administration reveals a differential role of pontine reticular formation and periaqueductal gray neurons in generation of the convulsive behaviors of audiogenic seizures

Abstract

The ventrolateral periaqueductal gray (PAG) and pontine reticular formation (PRF) are implicated in the neuronal network for audiogenic seizures (AGS). The AGS of genetically epilepsy-prone rats (GEPR-9s) culminate in tonic hindlimb extension (TE), and elevated acoustically evoked neuronal firing and burst firing, immediately preceding TE, have been observed in PAG and PRF. This study examined changes in PAG and PRF neuronal firing and behavior in GEPR-9s, following phenytoin administration. Recordings involved 16 PAG and nine PRF neurons in GEPR-9s. Phenytoin in doses (mean, 6.3 mg/kg) that suppressed TE selectively did not consistently alter PAG neuronal firing. However, these doses of phenytoin resulted in significant (51.6% of control) suppression of PRF neuronal firing. Doses of phenytoin (mean, 8.3 mg/kg), which completely blocked AGS, significantly reduced PAG neuronal firing (64.6% of control), and more greatly suppressed PRF firing (25.8% of control). These results are consistent with a critical role for PRF neurons in generation of TE not evident for PAG. The suppression of PAG and PRF neuronal firing induced by phenytoin with complete seizure blockade is consistent with vital roles for both structures in the seizure network. The differential effects of phenytoin on structures requisite to the seizure network indicate that this experimental approach may be able to identify the most sensitive therapeutic target for anticonvulsant drugs, which could be critical to pharmacological suppression of specific seizure behaviors manifest in various types of convulsions, potentially including human epilepsy.