| 10:10 am – 11:00 am | Trophic Factors in the Establishment and Maintenance of Seizure Disorders James O. McNamara, MD Abstract: The receptor tyrosine kinase, TrkB, is critical to diverse functions of the mammalian nervous system in health and disease. Evidence of TrkB activation in the mossy fiber pathway during epileptogenesis in vivo despite genetic deletion of its prototypic neurotrophin ligands led us to seek alternative ligands that might activate TrkB. The presence of high concentrations of the eivalent cation, zinc, in the mossy fibers together with evidence that zinc can transactivate the EGF receptor led us to hypothesize zinc, can transactivate TrkB. We found that zinc activates synaptic TrkB through increasing Src family kinase activity by an activity-regulated mechanism independent of neurotrophins. Further zinc potentiates the mossy fiber CA3 synapse by a TrkB dependent mechanism. The activitydependent activation of synaptic TrkB in a neurotrophin-independent manner provides a novel mechanism by which this receptor can regulate synaptic plasticity. |
| 11:00 am – 11:50 am | Technological Approaches to the Study of Epilepsy in Children Hal Blumenfeld, MD, PhD Abstract: In epilepsy there is a spectrum of levels of consciousness, which may be explained in terms of different states of brain activity. Ongoing studies in my laboratory include experiments to explore network mechanisms common to seizures and other states of impaired consciousness. In particular, we are investigating the role of cortical and subcortical structures such as the thalamus and brainstem in the propagation and behavioral manifestations of seizures. Current projects include: 1. In vivo electrophysiology and fMRI recordings from animal models of epilepsy, 2. Molecular studies of changes in seizure-prone brain regions, and 3. Human neuroimaging and electrophysiology studies of epilepsy-induced loss of consciousness. |