Absence epilepsy is a disorder of childhood that causes brief periods of unresponsiveness associated with a disruption of the normal rhythms of thought, which can interfere with a child's ability to learn. Absence seizures are characterized electroencephalographically by low-frequency, high-voltage spike-wave rhythms that involve the thalamus. Of the major seizure types, absence epilepsy is unusual in that it often can be triggered by repetitive visual stimulation. The long-term goal of this research is to use computer models based on detailed physiology of intrinsic neuronal properties and synaptic connectivity to explain the genesis of normal and pathological slow rhythms of the thalamus. We use computer models as a framework for integrating new physiological and pharmacological observations. Current models of slow oscillations in the thalamus involve interactions between thalamic reticular nucleus cells and thalamocortical cells, synchronized by cortical input. We propose that visually evoked seizures could occur through a similar mechanism, with repetitive retinal drive providing an initial synchronizing influence, partially mediated by thalamic interneurons. Even without retinal driving, the connectivity of thalamic interneurons, their large numbers, and their ability to generate slow intrinsic oscillations lead us to believe that they will be involved in slow rhythms in the thalamus. The goal of this phase of study is to define critical intrinsic properties of interneurons and to reveal how this cell type interacts with other neural elements in the oscillatory circuitry. We will combine computer modeling and in vitro physiological recording under normal conditions and during pharmacological blockade to determine how the specific ion channels of these cells produce oscillations. We will also conducted detailed computer models, incorporation both passive and active processes to assess how information is transmitted from one part of the interneuron to the other and to thalamocortical cells. Finally, we will assess the in vitro responses of interneurons and thalamocortical cells to protocols that mimic established models of absence epilepsy.
| Uhlrich, D J; Manning, K A; O'Laughlin, M L et al. (2005) Photic-induced sensitization: acquisition of an augmenting spike-wave response in the adult rat through repeated strobe exposure. J Neurophysiol 94:3925-37 |
