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Mark E. Domroese    1991-2001
Staff Physician
Gunderson Clinic in Lacrosse, WI

Concordia College 1989

Neuroscience PhD 1998
Lewis B Haberly
Features of inhibitory neuronal circuitry in rat piriform cortex with implications for temporal lobe epileptogenesis and normal function
 
The piriform cortex has been implicated in temporal lobe epileptogenesis in several animal models. Studies in vivo have shown that the threshold for initiating temporal lobe seizures by injection of convulsants is much lower in the deep part of rostral piriform cortex (pre-endopiriform region) than in all other temporal lobe structures, and that seizures originating in this region are spread by way of the piriform cortex. Studies in vitro have revealed that the entire endopiriform region is highly epileptogenic. A particularly intriguing finding is that different forms and stages of seizure activity in the endopiriform-piriform region occur in highly localized subregions. The present studies were undertaken with the rationale that this physiological segregation will be reflected in differences in inhibitory neuronal circuitry, and that characterization of these differences will provide insight into mechanisms of epileptogenesis. Inhibitory neuronal circuitry was visualized with antisera to GABA, a GABA transporter (GAT-1), enzymes found in GABAergic cells (GAD-65, GAD-67, nitric oxide synthase), and calcium binding proteins (parvalbumin, calbindin, calretinin) and neuropeptides (NPY, CCK, VIP) that are commonly co-localized with GABA. The results revealed a surprisingly large number of different neuron populations and fiber systems in the endopiriform nucleus and adjoining deep piriform regions. Of particular interest are the following: (1) A new nucleus was discovered at the center of the deep piriform region from which temporal lobe seizures are readily evoked; this nucleus displays a number of features that could promote epileptogenesis including a very low level of GAT-1 and an apparent absence of inhibitory endings on axon initial segments. (2) The region of the endopiriform nucleus where epileptiform activity originates in slices taken from rats with experimentally induced epilepsy (onset site) has a very low density of inhibitory basket endings on cell bodies and a unique, very dense calretinin containing fiber system that is believed to be excitatory. (3) The region of the endopiriform nucleus recently shown to generate abnormal plateau activity that precedes the development of paroxysmal activity at the onset site has unique circuitry features including distinctive neuron populations that contain NPY, NOS, and parvalbumin.
 
Thesis Publications

  • Ekstrand JJ, Domroese ME, Feig SL, Illig KR, Haberly LB. Immunocytochemical analysis of basket cells in rat piriform cortex. J Comparative Neurol 434:308-328, 2001.
  • Ekstrand JJ, Domroese ME, Johnson DM, Feig SL, Knodel SM, Behan M, Haberly LB. A new subdivision of anterior piriform cortex and associate deep nucleus with novel features of interest for olfaction and epilepsy. J Comparative Neurol 434:289-307, 2001.