Recruitment of interictal- and ictal-like discharges in posterior piriform cortex by delta-rate (1–4 Hz) focal bursts in anterior piriform cortex in vivo

Abstract

The development and propagation of seizure-related activity was studied in piriform cortex (PC) and areas in the medial temporal lobe to which it projects. In the urethane anesthetized adult rat at normal body temperature, tiny injections of convulsants in anterior PC (APC) generate an epileptogenic zone (focus) that can recruit electrographic seizures in untreated posterior PC (PPC) when bursts in the focus are paced at delta frequency (1–4 Hz) by stimulating the lateral olfactory tract. Epileptiform activity initiated by this ‘paced-recruitment’ procedure propagates throughout PPC and into other areas involved in mesial temporal lobe epilepsy (mTLE) at an exceedingly low velocity (< 1 mm/sec) as reported for focal seizures in human cortex. Proconvulsants increased the probability of recruiting electrographic seizures relative to disinhibiting agents that typically recruited interictal discharges. Through methods including realtime recording of current source-density (CSD) with vertical 22-site silicon-based electrodes, and membrane potential with transmembrane microelectrode pairs, insights were gained into mechanisms for epileptogenesis from PC. These findings also may apply to seizure initiation from epileptogenic zones in other areas that project to PPC in addition to APC. Findings from surgical studies indicating that PC plays a critical role in mTLE suggest that the results may be relevant to finding new approaches for blocking seizures from this common, virulent form of epilepsy. Immediate implications for treatment include the optimal placement and patterning of deep brain stimulation to increase its effectiveness for blocking seizures from mTLE while reducing the risk to vasculature from direct stimulation of PC.