Abstract
Neuronal exocytosis facilitates the propagation of information through the nervous system pertaining to bodily function, memory, and emotions. Using amperometry, the sub-millisecond dynamics of exocytosis can be monitored and the modulation of exocytosis due to drug treatment or neurodegenerative diseases can be studied. Traditional single-cell amperometry is a powerful technique for studying the molecular mechanisms of exocytosis, but it is both costly and labor-intensive to accumulate statistically significant data. To surmount these limitations, we have developed a silicon-based electrode array with 1024 on-chip electrodes that measures oxidative signal in 0.1 millisecond intervals. Using the developed device, we are able to capture the modulation of exocytosis due to Parkinson’s disease treatment (L-Dopa), with statistical significance, within 30 total minutes of recording. The validation study proves our device’s capability to accelerate the study of many pharmaceutical treatments for various neurodegenerative disorders that affect neurotransmitter secretion to a matter of minutes.
Highlights
Neuronal exocytosis facilitates the propagation of information through the nervous system pertaining to bodily function, memory, and emotions
Neurotransmitters are released in quantal events through a fusion pore, which are created when vesicles fuse with the plasma membrane during the exocytosis process
The prohibitive features of single-cell amperometry have limited the wide application of this technology to survey the molecular effects of pharmacological modulations and neurodegenerative pathologies associated with the synaptic neurotransmitter secretion process
Summary
Neuronal exocytosis facilitates the propagation of information through the nervous system pertaining to bodily function, memory, and emotions. Traditional single-cell amperometry is a powerful technique for studying the molecular mechanisms of exocytosis, but it is both costly and labor-intensive to accumulate statistically significant data To surmount these limitations, we have developed a silicon-based electrode array with 1024 on-chip electrodes that measures oxidative signal in 0.1 millisecond intervals. Despite the significance of the studies conducted and the discoveries made using amperometry, the CFE technique is laborintensive[16,17,18,19,20,21,22], time consuming[19,23,24,25], and can take from weeks to several months[26] to research the effects of neurological diseases or pharmacological treatments In these studies, it is important that amperometry is performed at the single-cell level to account for heterogeneity in the characteristics of quantal release among the cell population[3,27]. Using the 10 × 10 electrode array, the effects of the antidepressant drugs, bupropion and citalopram, on neurotransmitter secretion have been studied[26]
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