The """"""""area tempestas"""""""" (AT) is an epileptogenic trigger site within the deep prepiriform cortex from which convulsive seizures are elicited in response to the focal application of low doses of GABA antagonists or glutamate agonists. In this proposal, neuroanatomical tract-tracing techniques and immediate early gene (IEG) expression will be used to map the anatomical substrates and monitor the functional changes associated with seizures evoked from the AT. First, the afferents and efferents of the area tempestas, using recently developed anterograde and retrograde tracers, will be mapped. Next, changes in regional c-fos expression selectively related to AT-evoked seizure activity will be determined. This will be distinguished from changes associated with (a) subconvulsive activation f the same pathways and (b) convulsive seizure activity evoked from (and limited to) brainstem circuits. Moreover, seizure progression will be prevented by inhibitory manipulations in substantia nigra in order to evaluate changes in c-fos expression associated with direct effects of AT stimulation unrelated to propagated seizure activity. To examine the circuitry and receptor mechanisms mediating seizure-evoked changes in c-fos expression, drugs (e.g., NMDA antagonists) will be applied to the target areas of the AT in an attempt to block the local and downstream changes in c-fos expression. In addition to c-fos, expression of other IEG such as zif-268, jun-B and c-jun will be examined. These studies are expected to provide us with an understanding of (1) the circuitry involved in generating convulsive seizures triggered from the deep prepiriform cortex, (2) the neurotransmitter receptor mechanisms mediating seizure-evoked changes in IEG expression in selected limbic targets and (3) the location and magnitude of changes in IEG expression specific to convulsive seizure activity as differentiated from subconvulsive activation of the same pathways.
| Dorsey, Charles H; Cousin, Carolyn E; Lewis, Fred A et al. (2002) Ultrastructure of the Schistosoma mansoni cercaria. Micron 33:279-323 |
