The Functional State of Glutamate- and GABA-Ergic Neurons in the Inferior Colliculi of Krushinsky–Molodkina Rats at Early Stages of Epileptogenesis

Abstract

Disturbances in the neurotransmitter systems associated with the development of temporal lobe epilepsy (TLE) have been well-studied in forebrain structures including the temporal cortex, amygdala, and hippocampus. It is known that in rodents genetically prone to audiogenic seizures, TLE establishment induced by audiogenic kindling is also associated with the involvement of the forebrain, however, initially epileptiform activity arises in the brainstem, in particular, in the inferior colliculi (IC). It is reasonable to suppose that neurochemical alterations in the IC may contribute significantly to the spreading of epileptiform activity at early steps of TLE development. At the same time, the functional state of the key neurotransmitter systems in the IC of audiogenic rodents exposed to audiogenic kindling remains unknown. In the present work, we performed a comprehensive analysis of proteins involved in glutamate- and GABA-ergic transmission in the IC of Krushinsky–Molodkina (KM) rats genetically prone to audiogenic seizures. A modified audiogenic kindling protocol was used to reproduce the early stage of TLE development. According to this protocol, rats were exposed to daily audiogenic stimulations for seven days. Naive KM rats were used as a control. Although the rodent’s predisposition to audiogenic seizures is often associated with the impairment of GABAergic transmission, no significant changes were found in the expression of GABA synthesis enzymes and GABA_A receptor α1 subunit in the IC of KM rats either 24 hours or a week after their last seizure. However, 24 hours after the last audiogenic stimulation, an increase in glutamatergic transmission in the IC was observed including upregulation of ERK 1/2 kinases, synaptic proteins synapsin 1 and SV2B, VGLUT1 and VGLUT2. One week after the last seizure, only an increase in VGLUT1 content in the IC was observed, suggesting the persistent changes in the neurons of forebrain structures, in particular, of the temporal cortex.