The network involved in the initiation and propagation of limbic motor seizures evoked from the deep prepiriform cortex will be explored using anatomical, pharmacological and neurophysiological approaches. Particular emphasis will be on defining the role of glutamate transmission in the primary targets of area tempestas (AT) an epileptogenic site within the prepiriform cortex. These targets include the posterior piriform cortex (PPC) and perirhinal cortex (PRC), the olfactory bulb (OB), and the superficial layers of prepiriform cortex (SLP). The hypotheses to be tested are that 1) glutamate transmission (particularly mediated via non-NMDA receptors) in PRC and PPC is crucial for mediating AT-evoked convulsive seizures; 2) inhibition of glutamate transmission bilaterally in PRC or PPC will protect against clonic convulsive seizures evoked by systemically administered bicuculline, kainic acid and pilocarpine; 3) AT sends direct excitatory projections to PPC and PRC, some of which are glutamatergic; 4) blockade of glutamate receptors focally in PPC, PRC and OB will prevent the seizure-evoked increases in c-fos mRNA in these regions; 5) the OB is a source of excitatory amino acid containing projections to AT as well as a target of excitatory projections from AT; and 6) excitatory input to SLP from AT can induce paroxysmal depolarization shifts and related bursting in SLP neurons and that EAA transmission mediates these responses in SLP. These hypotheses will be treated using focal applications of selectively- acting drugs in vivo and, where applicable, by application of drugs or electrical stimulation in brain slices maintained in vitro. Behavioral, electroencephalographic, and single unit recordings will be made in order to monitor seizure activity and neural interactions in vivo, whereas whole-cell patch clamp and field potential recording will be conducted in brain slices. These studies are expected to provide important insights into the role of NMDA and non-NMDA transmission in the genesis and propagation of forebrain seizures. By combining in vivo and in vitro approaches we hope to begin to bridge the existing gap between the analysis of the pharmacology of EAA transmission in local circuits and that of long distance circuits in the limbic system as related to epileptogenesis.