BMI Seminar // Abnormal release of neurotransmitter and Ca2+ influx in presynaptic terminals in cortical neurons of a knock-in mouse model of Huntington’s disease
Event details
Date | 30.08.2017 |
Hour | 12:15 › 13:15 |
Speaker | Hyokeun Park, Division of Life Science, Hong Kong University and Technology, Hong Kong, China |
Location | |
Category | Conferences - Seminars |
Hong Kong
Huntington’s disease (HD) is a genetic neurodegenerative disorder caused by an abnormal expansion of CAG trinucleotide repeats in the huntingtin gene. Mutant huntingtin (mhtt) proteins induce the progressive neuronal loss from the striatum and cortex, despite of their ubiquitous expression. One possible mechanism of this selective degeneration is that dysfunction in synaptic transmission in the corticostriatal synapses could lead to the selective degeneration of these striatal neurons. However, the release of neurotransmitters as an input of corticostriatal synapses in HD has not fully understood yet. Thus we examined (or estimated) the release of neurotransmitters and the influx of Ca2+ during the stimulation at single presynaptic terminals in primary cortical neurons using real-time imaging with FM 1-43 labeled synaptic vesicles and Cal-520 (an ultrasensitive Ca2+ indicator). The released neurotransmitters at presynaptic terminals in heterozygous neurons of a HD knock-in mouse model (Q175) were significantly higher than wild-type neurons. The influx of Ca2+ in presynaptic terminals (distal from cell bodies) in heterozygous neurons was significantly higher compared with wild-type, implying that higher Ca2+ increase release of neurotransmitters in HD. The abnormal increase was rescued by the application of Ca2+ chelators and N-type voltage-gated Ca2+ channel blockers. Our results suggest that the increased release of neurotransmitter caused by higher influx of Ca2+ in presynaptic terminals of cortical neurons contribute to damage striatal and cortical neurons, which may underlie the selective neurodegeneration in HD.
Practical information
- Informed public
- Free
Organizer
- SV BMI Host : L. Lashuel