Investigations of Seizure Propagation Directionality: Effects of Temperature and GABAergic Disinhibition

<p>Epilepsy is one of the most common neurological disorders, affecting approximately 3% of the population. By understanding the mechanisms through which foci and seizure pathways develop, more precise therapies and fuller understandings of cortical connectivity can be developed. The studies in this paper examine hemispheric dominance, and seizure propagation in mouse in vitro cortical-slice preparations. The primary goals of these experiments are 1) to describe the relationship between inhibitory neurotransmitters and the development of stereotyped propagation 2) to describe how these biological phenomena relate to applied heat, and 3) to test the relevance of describing our experimental models as coupled oscillators.</p> <p>We found that large-scale bath-temperature increase (~7°C) will globally amplify seizure genesis, and that small (<0.1°C) temperature differences between hemispheres can produce a significant effect on the relative dominance between hemispheres. However, this small amount of heat alone is not sufficient to significantly alter the rate of local epileptiform-like event (EEs) generation in cortex. While a dominant hemisphere almost always develops in a bicuculline treatment, heat effect which hemisphere becomes dominant. Non-dominant hemispheres have a significantly lower oscillatory rate after an hour of Bic treatment, suggesting that callosal projections are necessary for the emergence of this difference. GABA_B was antagonized with CGP in an attempt reduce the disparity of oscillatory rates between hemispheres through the occlusion of feed-forward inhibition. While CGP was shown to have negligible effects on directionality, it did surprisingly have the significant effect of reducing the number of EEs generated. CGP also increased the velocity at which EEs traveled, reduced the number of unilateral events, and reduced the effect of small-scale local heat application on hemispheric dominance. While precise mechanisms through which directionality and interhemispheric dominance develop are unknown, these data give interesting insight into the effects that functional GABA_B currents have on the reduction of interhemispheric EE efficacy and the early stages of the development of hemispheric dominance. Our analysis of mono-hemispheric IHL and unilateral rates also give promising insight into the attributes of a dominant hemisphere.</p> <p>Describing our preparation as a pulse-coupled oscillator without an a priori leader appears to be accurate, as hemispheres with drastically different oscillatory rates can produce synchronous activity.</p>