Cellular and molecular substrates of epileptiform activity in the amygdala

Die Projektionsneurone (PN) des lateralen Amygdala (LA) spielen eine kritische Rolle in der Pathogenese der humanen Temporallappen-Epilepsie (TLE); ihre präzise Beteiligung an der Generierung, Ausprägung und Verlauf epileptischer Erkrankungen ist bisher jedoch nur lückenhaft untersucht. Diese Studie zielte darauf ab der Hypothese nachzugehen, daß glutamaterge Mechanismen während der Entwicklung epileptischer Anfälle bei der TLE verändert sind. Zu diesem Zweck wird hier das sog. Pilokarpin-Mausmodells verwendet, um die intrinsichen und synaptischen Eigenschaften von PN der LA in Abhängigkeit von der epileptischen Anfallsaktivität zu analysieren. Hinsichtlich der TLE zeigt diese Studie: - dynamische Veränderungen in der glutamaterge Transmission - eine differentielle NMDA-Rezeptor-Beteiligung an den Veränderungen während der latent und chronische Phasen der Epilepsie - eine Erhöhung des Exzitations/Inhibitions-Verhältnisses während der beiden Untersuchten Phasen der Epilepsie

Directional spread of activity in synaptic networks of the human lateral amygdala.

Spontaneous epileptiform activity has previously been observed in lateral amygdala (LA) slices derived from patients with intractable-temporal lobe epilepsy. The present study aimed to characterize intranuclear LA synaptic connectivity and to test the hypothesis that differences in the spread of flow of neuronal activity may relate to spontaneous epileptiform activity occurrence. Electrical activity was evoked through electrical microstimulation in acute human brain slices containing the LA, signals were recorded as local field potentials combined with fast optical imaging of voltage-sensitive dye fluorescence. Sites of stimulation and recording were systematically varied. Following recordings, slices were anatomically reconstructed using two-dimensional unitary slices as a reference for coronal and parasagittal planes. Local spatial patterns and spread of activity were assessed by incorporating the coordinates of electrical and optical recording sites into the respective unitary slice. A preferential directional spread of evoked electrical signals was observed from ventral to dorsal, rostral to caudal and medial to lateral regions in the LA. No differences in spread of evoked activity were observed between spontaneously and non-spontaneously active LA slices, i.e. basic properties of evoked synaptic responses were similar in the two functional types of LA slices, including input-output relationship, and paired-pulse depression. These results indicate a directed propagation of synaptic signals within the human LA in spontaneously active epileptic slices. We suggest that the lack of differences in local and in systemic information processing has to be found in confined epileptiform circuits within the amygdala likely involving well-known 'epileptic neurons'