Altered exocytosis of inhibitory synaptic vesicles at single presynaptic terminals of cultured striatal neurons in a knock-in mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive dominantly inherited neurodegenerative disease caused by the expansion of a cytosine-adenine-guanine (CAG) trinucleotide repeat in the gene, which encodes the mutant huntingtin protein containing an expanded polyglutamine tract. One of neuropathologic hallmarks of HD is selective degeneration in the striatum. Mechanisms underlying selective neurodegeneration in the striatum of HD remain elusive.

Alterations of presynaptic proteins in autism spectrum disorder.

The expanded use of hypothesis-free gene analysis methods in autism research has significantly increased the number of genetic risk factors associated with the pathogenesis of autism. A further examination of the implicated genes directly revealed the involvement in processes pertinent to neuronal differentiation, development, and function, with a predominant contribution from the regulators of synaptic function. Despite the importance of presynaptic function in synaptic transmission, the regulation of neuronal network activity, and the final behavioral output, there is a relative lack of understanding of the presynaptic contribution to the pathology of autism.

Single vesicle tracking for studying synaptic vesicle dynamics in small central synapses.

Sustained neurotransmission is driven by a continuous supply of synaptic vesicles to the release sites and modulated by synaptic vesicle dynamics. However, synaptic vesicle dynamics in synapses remain elusive because of technical limitations. Recent advances in fluorescence imaging techniques have enabled the tracking of single synaptic vesicles in small central synapses in living neurons.

Precise and long-term tracking of mitochondria in neurons using a bioconjugatable and photostable AIE luminogen.

Tracking mitochondrial movement in neurons is an attractive but challenging research field as dysregulation of mitochondrial motion is associated with multiple neurological diseases. To realize accurate and long-term tracking of mitochondria in neurons, we elaborately designed a novel aggregation-induced emission (AIE)-active luminogen, TPAP-C5-yne, where we selected a cationic pyridinium moiety to target mitochondria and employed an activated alkyne terminus to achieve long-term tracking through bioconjugation with amines on mitochondria. For the first time, we successfully achieved the accurate analysis of the motion of a single mitochondrion in live primary hippocampal neurons and the long-term tracking of mitochondria for up to a week in live neurons.

Unique dynamics and exocytosis properties of GABAergic synaptic vesicles revealed by three-dimensional single vesicle tracking.

Maintaining the balance between neuronal excitation and inhibition is essential for proper function of the central nervous system. Inhibitory synaptic transmission plays an important role in maintaining this balance. Although inhibitory transmission has higher kinetic demands compared to excitatory transmission, its properties are poorly understood.