The """"""""area tempestas"""""""" is an epileptogenic trigger site within the deep prepiriform cortex that our laboratory has recently defined and characterized. This site, highly restricted anatomically, contains GABAergic, cholinergic and excitatory amino acid-mediated synapses which interact to control seizure initiation. Activation of the NMDA-preferring subtype of excitatory amino acid receptors appears necessary for eliciting seizures from this site by either GABA antagonists or muscarinic agonists. As NMDA receptors function to activate the final common epileptogenic output of area tempestas, this locus is an ideal model system in which to evaluate the ability of drugs to influence convulsant mechanisms via actions on excitatory amino acid transmission in vivo. Accordingly, we intend to utilize this model system to: 1. Evaluate competitive and noncompetitive antagonists for NMDA-sensitive receptors in terms of their anticonvulsant action when focally applied to area tempestas; 2. Evaluate the effects of agents that interact with modulators of excitatory amino acid receptors (glycine and quisqualate); 3. Evaluate systemic seizure models (induced by pentylenetetrazol, kainic acid, beta-carboline) for their sensitivity to inhibition by interference with excitatory amino acid transmission in area tempestas; 4. Determine whether the olfactory bulbs represent an important source of excitatory amino acid-containing afferents to area tempestas; 5. Determine the effect of convulsive seizures evoked from area tempestas on regional c-Fos gene expression in brain. These studies will provide information fundamental for understanding some of the neurochemical circuitry engaged in the initiation and control of limbic- related motor seizures, and, at the same time, should expand our understanding of the functional impact of drugs capable of influencing various aspects of excitatory amino acid neurotransmission.
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