Melissa A. Harrington, PhD
Professor of Biology
Delaware State University
Melissa Harrington, PhD My research focuses on the functional development of motor neurons and how that development goes awry in motor neuron disease. Historically, studies of motor neurons have revealed many fundamental properties of neurons and neuronal signaling that apply to all neurons. These include understanding how synapses are formed, how they function, and how synaptic maps are established and refined. An interesting property of motor neurons is that they make synapses of two very different types: the neuromuscular junction that drives muscle contraction in the periphery; and the synapses on other neurons in the spinal cord that modulate motor reflexes and coordinate muscle activation. Since the 1940s, it has been known that motor neurons release acetylcholine as the neurotransmitter at the neuromuscular junction, however, multiple recent studies have demonstrated that motor neurons express markers for glutamatergic transmission and that the connections motor neurons make on other neurons in the spinal cord include synapses releasing glutamate as well as acetylcholine. Thus it appears that motor neurons are capable of spatially segregating neurotransmitter release between two types of synapses that they make – releasing acetylcholine at the neuromuscular junction and some combination of glutamate and acetylcholine at synapses on other neurons.
Harrington Research (1)
The long-term goal of my lab is to understand how motor neurons complete their development and form active synapses of two different types that differ in the neurotransmitter released. My lab uses electrophysiological techniques to investigate factors important for controlling development and expression of the neurotransmitter phenotype of motor neurons. Specifically, we use multi-electrode array recording with a 64 electrode array as well as whole-cell patch clamp recording of individual motor neurons. We are recording from motor neurons isolated from the spinal cord of mouse embryos and grown in primary culture, as well as recording motor neurons in slices of the spinal cords from neonatal mouse pups.
Harrington Research
Another project in my lab focuses on investigating how the process of forming active synapses goes awry in the neuromuscular disorder spinal muscular atrophy (SMA). SMA is the most common inherited cause of infant mortality. In SMA, loss of the survival motor neuron 1 (SMN1) gene leads to dysfunction in spinal motor neurons and muscle atrophy. In spite of more than a decade of research with mouse models of the disease, the SMA Mousepathophysiology of SMA remains poorly understood. In the mouse models of the disease, there is minimal motor neuron loss in the early stages of the disease even though the mice have severe motor behavioral abnormalities. In addition, in the early stages, muscles that are structurally fully innervated by motor neurons fail to grow. This suggests that the disease is not simply the result of death of motor neurons, but a loss of function.Harrington Research
Lab StudentsData from our lab and others suggest that SMN-deficient motor neurons have altered excitability which may impair their function, however the time of onset of the changes and their relationship to symptom development are not known, and it is not clear whether they results from intrinsic physiological abnormalities of motor neurons themselves or altered synaptic input. Our is investigating some important, unanswered questions about the pathophysiology of SMA: 1) How is motor neuron excitability altered by SMN deficiency? 2) What is the nature of this abnormality and when does it occur? and 3) Do the abnormalities arise from a cell-autonomous process in motor neurons or does impaired synaptic input from SMN deficient neurons presynaptic to motor neurons play a significant role?
Return to Previous Page