| Abstract No.: | A-C1078 |
| Country: | Canada |
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| Title: | SEIZURES IMPEDE DENDRITIC GROWTH - IN VIVO IMAGING OF THE DEVELOPING BRAIN |
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| Authors/Affiliations: | 1 D. Sesath Hewapathirane; 1 Chen Simon; 1 Dunfield Derek; 1 Wesley Yen;
1 University of British Columbia, Vancouver, BC, Canada
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| Content: | Objectives: The immature brain is exceptionally epileptogenic with the highest incidence of seizures in humans occurring during the first years of life. While these seizures occur during critical periods of synaptogenesis and neuronal growth, little is known of the impact of neonatal seizures on brain circuit development.
Methods: We have developed and characterized a novel model system designed specifically to examine effects of experimentally induced seizures on the growth of neurons within the intact developing brain. This model system involves pentylenetetrazol (PTZ)-induced seizures in the albino Xenopus laevis tadpole and in vivo two-photon time-lapse imaging of individual immature neurons fluorescently labeled by single-cell electroporation.
Results: Bath application of PTZ elicits reproducible behavioural and electrographic seizures that cease upon washout of PTZ or by application of anticonvulsants. PTZ-induced seizure activity is highly comparable to that observed in commonly utilized mammalian seizure models, as revealed by detailed analysis of behavioural seizures, extracellular electrophysiological recording in vivo, and imaging of neuronal network dynamics in vivo using Calcium-sensitive fluorescent indicators. Rapid time-lapse imaging of fluorescently labeled individual developing neurons, within un-anaesthetized immobilized tadpoles during seizures, revealed that dendritic filopodia – dynamic structural processes involved in dendrite growth – are significantly less motile and have a significantly higher retraction rate as compared to controls. Imaging of the entire dendritic arbor of growing neurons over 8 hours revealed that prolonged seizures impede overall dendritic arbor growth, and that more sustained seizure activity eventually leads to retraction of existing dendritic branches. We next examined whether the observed short-term effects on dendritic growth during neuronal development led to a permanent change in the size and shape of the mature dendritic arbor. Neurons that experienced a single seizure event (1 hour duration) during their development showed significantly reduced total dendritic size upon maturation, suggesting that seizure-induced effects are persistent.
Conclusions: Collectively, these results demonstrate that seizures impede neuronal growth within the developing brain, and describe changes in growth dynamics that underlie these effects. Our findings are particularly important given that the observed anatomical changes likely affect neuronal function and connectivity. Future directions include identifying the molecular signals underlying the observed changes, and examining seizure-induced effects on synapse formation and stability. |
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