Changes in the behavior and oscillatory activity in cortical and subcortical brain structures induced by repeated l-glutamate injections to the medial septal area in guinea pigs

- Oscillations in various brain areas were sensitive to septal injections of l-glutamate.
- Repeated daily medial septal infusion of l-glutamate evoked epileptogenesis.
- The earliest sign of seizure pathology was the disturbances of high frequency (presumable ripples) oscillations.
- We argue that septal glutamatergic system can participate in epilepsy development.

Although the presence and importance of oscillations in cortical structures is well-documented, little is known about this rhythmic activity in subcortical areas. In waking guinea pigs, during their inattentive rest, local field potentials (LFPs) were recorded simultaneously in eight brain structures. In the cortical areas (prefrontal and entorhinal fields, hippocampus, dentate gyrus) and subcortical ones (medial and lateral septal nuclei, central nucleus of amygdala, and supramammillary nucleus), different types of oscillations were observed: delta (0.5-4 Hz), theta (4-8), alpha (10-12), gamma (40-80), and high-frequency, presumable ripples (100-200 Hz). In all structures, low-frequency oscillations (delta and theta) were more powerful than high-frequency ones. Structural communications in different bands of rhythmic activity were expressed differently. On the whole they were the more intensive, the stronger were the oscillations, however, this was not the absolute rule. A long-term (about a month) daily injection of l-glutamate into the medial septal region induced significant changes in theta, gamma, and high-frequency oscillations in most regions examined. The correlations of some structures also changed; they significantly decreased between the entorhinal cortex and hippocampus in the theta band and between the medial septum and central amygdala in the gamma band. During permanent septal glutamate infusion, distinct signs of epileptogenesis were revealed (epileptiform activity, seizure behavior of animals, and formation of aberrant fibers in the hippocampus). Thus, we believe that the glutamatergic system of medial septum can participate in the development of epilepsy. The earliest sign of pathology in electrical activity was alterations in high-frequency oscillations in the dentate gyrus and medial septum, but the strongest changes were in theta and especially gamma rhythms in many structures. The data obtained help to advance our understanding of the basic mechanisms of brain functioning and its disturbances in seizure pathology.