Analysis of the State of Glutamate- and Gaba-Ergic Neurons in the Inferior Colliculi of Krushinsky – Molodkina Strain Rats at Early Stages of Epileptogenesis

Abstract

Disturbances in the neurotransmitter systems during the development of temporal lobe epilepsy have been most detailed studied in forebrain structures – in the temporal cortex, amygdala, and hippocampus [1, 2]. It is known that during the formation of temporal lobe epilepsy in the model of audiogenic kindling there is a spread of epileptiform activity from brainstem to forebrain structures. However, the molecular mechanisms of neurotransmission dysregulation in the inferior colliculi in rodents with genetic prone to audiogenic seizures during epileptogenesis remain unknown. Changes in neurotransmitter systems of inferior colliculi may contribute significantly to the recruitment of forebrain structures during the initial stages of epileptogenesis. The current work provides a comprehensive analysis of activity markers of glutamate- and GABA-ergic neurons in inferior colliculi of Krushinsky – Molodkina (KM) rats genetically prone to audiogenic seizures. A modified audiogenic kindling protocol was used to model the early stages of temporal lobe epilepsy development. In this protocol rats were subjected to daily audiogenic seizures for seven days. Naive KM rats were used as controls. Although the rodent’s predisposition to audiogenic seizures is often associated with disruptions in GABAergic transmission, no significant changes were found in the expression of GABA synthesis enzymes or the α1 subunit of the GABAA receptor in the brains of KM rats, either 24 hours or a week after their last convulsive seizure. However, 24 hours after the last audiogenic seizure, an increase in glutamatergic transmission in the inferior colliculi was observed: the activity of ERK 1/2 kinases and the exocytosis protein synapsin 1 increased, as well as the expression of VGLUT1 and VGLUT2 and the synaptic protein SV2B. One week after the last seizure, only an increase in VGLUT1 content in the inferior colliculi was observed, suggesting that persistent changes occur in the neurons of forebrain structures, in particular, the temporal cortex.