The neurodegenerative disease spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Children affected by SMA experience severe muscle weakness and are unable to sit up, walk or breathe.
Although much work has focused on understanding the changes that occur in motor neurons that lead to their degeneration and to paralysis, very little is known about the changes that occur in other neuron types or how changes in spinal or brainstem circuits could alter the survival and function of motor neurons in this disease.
We use a collection of transgenic mice to label or manipulate specific types of interneurons in order to assess how the connections between neurons deteriorate in mouse models of SMA and how this is important for disease. These studies will determine whether therapies that target motor circuits would be more effective than therapies that target motor neurons alone.
Our goal is to develop strategies to prevent neurodegeneration and/or improve the quality of life of SMA patients and their families.
Confocal image of motor neurons
(blue= choline acetyltransferase, red= IRF3)
and glutamatergic synapses (green)
in the ventral horn of the spinal cord.
Sensory afferent synapses (cyan)
contacting a V2a interneuron (green).