Assessing neuromuscular transmission in mice with Huntington's disease

Huntington???s disease (HD) is a degenerative genetic illness that is characterized by progressive and severe cognitive and motor dysfunction. The motor symptoms include chorea (involuntary movement), dystonia (sustained muscle contractions), rigidity (stiffness), and weakness. These symptoms are typically thought to be caused by neurodegeneration. Recently our laboratory has shown that there are defects in skeletal muscle in mice with HD. This project is focused on studying the signals sent from the brain to skeletal muscle, which occurs at the neuromuscular junction (NMJ). In particular, we are studying miniature end plate potentials (mEPPs) and evoked end plate potentials (eEPPs). These signals result in the release of acetylcholine packets from the presynaptic terminal to the postsynaptic terminal (causing a small depolarization). A mEPP results from the release of a single vesicle of acetylcholine. An eEPP results from the release of many vesicles of acetylcholine; this is caused by stimulation of the motor neuron. The signals within a muscle fiber are recorded by utilizing two intracellular microelectrodes, and a third isolated microelectrode for nerve stimulation. From this data, the mean number of vesicles released per nerve stimulation can be found; this is known as quantal content. Quantal content is calculated by taking the mean amplitude of eEPPs over the mean amplitude of mEPPs. By comparing the quantal content of HD mice to wild type mice, we can begin to determine if there are defects in the neuromuscular junction in HD