Comparison of intrinsic optical signals associated with low Mg2+- and 4-aminopyridine-induced seizure-like events reveals characteristic features in adult rat limbic system

Purpose: To analyze the intrinsic optical signal change associated with seizure-like events in two frequently used in vitro models-the low-Mg2+ and the 4-aminopyridine (4-AP) models-and to monitor regions of onset and spread patterns of these discharges by using imaging of intrinsic optical signals (IOS). Methods: Combined hippocampal-entorhinal-cortex slices of adult rats were exposed to two different treatments: lowering extracellular Mg2+ concentrations or application of 100 mu M 4-AP. The electrographic features of the discharges were monitored using extracellular microelectrodes. Optical imaging was achieved by infrared transillumination of the slice and analysis of changes in light transmission using a subtraction approach. The electrographic features were compared with the optical changes. Regions of onset and spread patterns were analyzed in relevant anatomic regions of the slice. Results: Both lowering extracellular Mg2+ concentrations and application of 4-AP induced seizure-like events. The relative duration of the intrinsic optical signal change associated with seizure-like events in the low-Mg2+ model was significantly longer compared with that seen with those occurring in the 4-AP model, although duration of field potentials did not differ significantly in the two models. Seizure-like events of the low-Mg2+ model originated predominantly in the entorhinal cortex, with subsequent propagation toward the subiculum and neocortical structures. In contrast, no consistent region of onset or spread patterns were seen in the 4-AP model, indicating that the seizure initiation is not confined to a particular region in this model. Conclusions: We conclude that different forms of spontaneous epileptiform activity are associated with characteristic optical signal changes and that optical imaging represents an excellent method to assess regions of seizure onset and spread patterns.