Almost 80% of adults diagnosed with polymicrogyria, a developmental abnormality of the cerebral cortex, have an associated seizure disorder (Barkovich and Kjos, 1992). Unfortunately, this form of epilepsy tends to respond poorly to surgery or medication. Now there is an animal model for microgyria that causes reproducible, focal, seizure-like activity (Dvorak and Feit, 1977; Jacobs et al., 1996). Small freeze lesions are made on the cortical surface of normal neonatal rats; these cause destruction of deep cortical layers and compression of the layers above, creating a dimple, or microgyrus once the cortex matures. The microgyrus produces epileptiform activity that can be measured in slices of lesioned neocortex in vitro. There is very little information about the synaptic and cellular mechanisms underlying chronically epileptic cortex. The goal of this proposal is to use the freeze lesion model to explore the synaptic and cellular changes that cause seizures. More specifically, we will record from identified pairs of excitatory and inhibitory neurons in layer V to look for 1) changes in the intrinsic membrane properties of individual neurons, and 2) changes in the synaptic coupling of excitatory-excitatory, excitatory-inhibitory, and inhibitory-inhibitory cell pairs. In addition, we will look for morphological changes in the axonal and dendritic branching patterns of the neurons involved in the generation of epileptiform activity. Finally, we will explore the role of a molecule known to promote dendritic arborization (cpg 15; Nedivi et al., 1993) by using in situ hybridization, and we will attempt to reverse any overarborization in the epileptic zone by viral vaccination with a truncated form. of cpg l5. In this way, we hope to elucidate some of the underlying mechanisms of hyperexcitability in microgyria, including the extent of synaptic and cellular reorganization.
| Landisman, Carole E; Connors, Barry W (2007) VPM and PoM nuclei of the rat somatosensory thalamus: intrinsic neuronal properties and corticothalamic feedback. Cereb Cortex 17:2853-65 |
| Patrick, Saundra L; Connors, Barry W; Landisman, Carole E (2006) Developmental changes in somatostatin-positive interneurons in a freeze-lesion model of epilepsy. Epilepsy Res 70:161-71 |
| Landisman, Carole E; Connors, Barry W (2005) Long-term modulation of electrical synapses in the mammalian thalamus. Science 310:1809-13 |
| Long, Michael A; Landisman, Carole E; Connors, Barry W (2004) Small clusters of electrically coupled neurons generate synchronous rhythms in the thalamic reticular nucleus. J Neurosci 24:341-9 |
