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

Disturbances in the neurotransmitter systems associated withthe development of temporal lobe epilepsy (TLE) have been well-studiedin forebrain structures including the temporal cortex, amygdala, andhippocampus. It is known that in rodents genetically prone to audiogenicseizures, TLE establishment induced by audiogenic kindling is alsoassociated with the involvement of the forebrain, however, initiallyepileptiform activity arises in the brainstem, in particular, inthe inferior colliculi (IC). It is reasonable to suppose that neurochemicalalterations in the IC may contribute significantly to the spreadingof epileptiform activity at early steps of TLE development. At thesame time, the functional state of the key neurotransmitter systemsin the IC of audiogenic rodents exposed to audiogenic kindling remainsunknown. In the present work, we performed a comprehensive analysisof proteins involved in glutamate- and GABA-ergic transmission inthe IC of Krushinsky–Molodkina (KM) rats genetically prone to audiogenicseizures. A modified audiogenic kindling protocol was used to reproducethe 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 toaudiogenic seizures is often associated with the impairment of GABAergictransmission, no significant changes were found in the expressionof GABA synthesis enzymes and GABA_A receptorα1 subunit in the IC of KM rats either 24 hours or a week aftertheir last seizure. However, 24 hours after the last audiogenicstimulation, an increase in glutamatergic transmission in the ICwas observed including upregulation of ERK 1/2 kinases, synapticproteins synapsin 1 and SV2B, VGLUT1 and VGLUT2. One week afterthe last seizure, only an increase in VGLUT1 content in the IC wasobserved, suggesting the persistent changes in the neurons of forebrainstructures, in particular, of the temporal cortex.