The Role of ERK1/2 Kinases in the Molecular Mechanisms of Regulation of Glutamatergic and GABAergic Neurons during the Development of Convulsive Seizures in Krushinskii–Molodkina Rats

The aim of the present work was to study the role of the ERK1/2 protein kinase cascade in regulating the activity of excitatory and inhibitory neurons in the hippocampus and temporal cortex in Krushinskii–Molodkina rats at the early stages of development of epileptiform convulsive seizures and at the ataxia stage. The content and distribution of study substances were assessed using an immunohistochemical method and western blot analysis. Levels of ERK1/2 kinase activity in the hippocampus increased significantly a few seconds after presentation of a sound signal, and this was accompanied by an increase in the content of SNARE protein, which is part of the SNAP25 complex, along with an increase in the activity of synapsin-1, which is responsible for vesicle release. Decreases in the content of the vesicular glutamate transporter (vGLUT2) on the background of increases in ERK1/2 activity and exocytosis proteins at the clonic-tonic stage of convulsive seizures constitute evidence for activation of glutamate release in the hippocampus, while decreases in ERK1/2 kinase activity and synapsin-1 in the temporal cortex, accompanied by an increase in vGLUT2, point to inhibition of glutamatergic neurotransmission. Decreased glutamate release activity in the temporal cortex thus appears to represent the origin of the decrease in the excitatory signal, which then leads to a reduction in glutamatergic system activity in the hippocampus at the ataxia stage, with termination of tonic convulsions and entry of the rats into the ataxia stage. These changes in the quantities and activities of proteins responsible for neurotransmitter release, correlating with changes in ERK1/2 activity, were most marked in glutamatergic neurons in the cortex and hippocampus. This leads to the conclusion that the kinases studied here have a predominant role in controlling glutamate release, thus taking part in the initiation of convulsive activity.