N. Charles Harata, MD, PhD
My laboratory focuses on the study of synaptic transmission in the mammalian central nervous system. Synapses are the sites at which electrical signals that have been transmitted through presynaptic neurons are converted to chemical signals (neurotransmitter release). The neurotransmitter released at these sites induces responses in the postsynaptic neuron – in the form of both electrical and chemical signals (such as an increase in the intracellular calcium concentration). The efficiency of this two-step information flow during synaptic transmission is vital to the control of neural network activity, and we are currently focusing on two projects related to this control of synaptic transmission.
In one project, we are evaluating the fundamental parameters of neurotransmitter release from the presynaptic site, including: the amount of neurotransmitter loaded into synaptic vesicles, and the variability in the rate of neurotransmitter release. We study them by applying the electrophysiological technology, live-cell wide-field fluorescence imaging, super-resolution fluorescence imaging and electron microscopy to the cultured brain neurons of wild-type rodents.
In another project, we are elucidating the cellular pathophysiology of a movement disorder dystonia. Dystonia is characterized by involuntary skeletal muscle contractions and abnormal postures. It causes extensive deterioration of the patient's quality of life. In some patients, this condition becomes life threatening (dystonic storm), with excessive muscle contractions leading to an inability to swallow or breathe, and to skeletal muscle breakdown and multi-organ failure. Unfortunately, there is no effective cure, and treatment options are limited. Our study addresses the synaptic abnormalities in the brain, especially in the rates of synaptic vesicle recycling and neurotransmitter release, the regulation of intracellular calcium signals, and the structures of synapses and intracellular organelles.