Epileptiform discharges with in-vivo-like features in slices of rat piriform cortex with longitudinal association fibers

Brain slices serve as useful models for the investigation of epilepsy. Howe ver, the preparation of brain slices disrupts circuitry and severs axons, t hus complicating efforts to relate epileptiform activity in vitro to seizur e activity in vivo. This issue is relevant to studies in transverse slices of the piriform cortex (PC), the preparation of which disrupts extensive ro strocaudal fiber systems. In these slices, epileptiform discharges propagat e slowly and in a wavelike manner, whereas such discharges in vivo propagat e more rapidly and jump abruptly between layers. The objective of the prese nt study was to identify fiber systems responsible for these differences. P C slices were prepared by cutting along three different nearly orthogonal p lanes (transverse, parasagittal, and longitudinal), and epileptiform discha rges were imaged with a voltage-sensitive fluorescent dye. Interictal-like epileptiform activity was enabled by either a kindling-like induction proce ss or disinhibition with bicuculline. The pattern of discharge onset was ve ry similar in slices cut in different planes. As described previously in tr ansverse PC slices, discharges were initiated in the endopiriform nucleus ( En) and adjoining regions in a two-stage process, starting with low-amplitu de "plateau activity" at one site and leading to an accelerating depolariza tion and discharge onset at another nearby site. The similar pattern of ons et in slices of various orientations indicates that the local circuitry and neuronal properties in and around the En, rather than long-range fibers, a ssume dominant roles in the initiation of epileptiform activity. Subtle var iations in the onset site indicate that interneurons can fine tune the site of discharge onset. In contrast to the mode of onset, discharge propagatio n showed striking variations. In longitudinal slices, where rostrocaudal as sociation fibers are best preserved, discharge propagation resembled in viv o seizure activity in the following respects: propagation was as rapid as i n vivo and about two to three times faster than in other slices; discharges jumped abruptly between the En and PC; and discharges had large amplitudes in superficial layers of the PC. Cuts in longitudinal slices that partiall y separated the PC from the En eliminated these unique features. These resu lts help clarify why epileptiform activity differs between in vitro and in vivo experiments and suggest that rostrocaudal pyramidal cell association f ibers play a major role in the propagation of discharges in the intact brai n. The longitudinal PC slice, which best preserves these fibers, is ideally suited for the study their role.