Muscle disorders of the masticatory systems, or neuromuscular dysfunction, has two major symptoms: pain and dysfunction. Millions of people are impacted by muscle fatigue, muscle tightness, myalgia, spasms, headaches, and decrease range of motion each year because of this disorder . Over the years, scientists have used many treatments to try to cure these muscle disorders, such as, drug therapies, physical and occupational therapies, surgery, and electrical stimulation. Although these treatments help, at present, there is no cure for most neuromuscular diseases, since scientist can not get to the exact point that causes the disorder. . Recently scientists have discovered advances in genetic engineering, which have provided alternative means to drug and occupational therapies. This alternative uses a combination of genetics and optics to control well-defined events within specific cells of living tissue, called optogenetics. It uses the insertion into cells of genes that confer light responsiveness and is associated with technologies for delivering light deep into organisms as complex as freely moving mammals, for targeting light-sensitivity to cells of interest .
Specific aim 1 will test the hypothesis that a focused ultrasound will help for targeted delivery of therapeutics to nerves in regions of the sciatic nerve. We can use dye-loaded microbubles to sciatic nerves, which have been previously used in vitro and in vivo. This will be assessed using microscopy, which will track the nerve using ultrasound imaging of targeted areas to assess risk of pressure related trauma. Also, the nerves will be electrically stimulated to observe the functional performance of the microbuble exposure .
Specific Aim 2 will apply focused ultrasound to specific static nerves using optical control in vivo. Electrical stimulation will be used for muscle stimulation for muscle control. The drawbacks of this, which include large fatigue of the motor units and the limit of therapeutic applications that are precisely opposite of the normal physiological recruitment patterns, will be tested. We will observe the enhanced performance and reduced fatigue of in vivo. We will find the point to an unanticipated new modality of neural control with broad implications for nervous system and neuromuscular physiology, as well as therapeutic innovation . Significance and Background
Optogenetics is the control over defined events within defined cell types at defined times a level of precision that is most likely crucial to biological understanding even beyond neuroscience.
The figure above shows how optogenetics works with the brain. The protein sampled from algea, ChR, which opens when blue light is shined on it, is inserted into DNA specific neurons in the brain. Electrical signals are sent during activation of the neuron, which can now be caused by the flash of a blue light..
It is very important to be exact in the time and measurements because even a shift of a few milliseconds in the timing of a neuron’s firing, for example, can sometimes completely reverse the effect of its signal on the rest of the nervous system, also, millisecond timing precision has been essential for key insights into both normal brain function and into clinical problems . Light responsive proteins are allows neurons to turn on or off selectively with unprecedented precision. When introduced to proteins, cultured cells or brains of live animals allow us to investigate the structure and function of neural networks . These optogenetic tools hold clinical promise, with the potential for modulating activity of brain circuits involved in neurological disorders or restoring vision loss.
Theses figures show the schematic representation of the action of channelrhodopsin and halorhodopsin on neural cells. “Activation with blue lights opens the channel (channelrhodopsin), allowing in sodium ions and turning the...
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