Development of in vitro micropatterned neuromuscular junctions – MIMETiC

The neuromuscular junction is a synapse that represents the basic structure by which the activity of spinal motoneurons controls muscle contraction or relaxation during movement. As existing in vitro models do not allow for adequate acquisition of major functional readouts, we propose to develop an innovative reconstruction of mature neuromuscular junctions that can be used to explore electrophysiological features of motoneuron-muscle synaptic transmission and/or to evaluate new drugs developed for the therapy of various neurodegenerative, neuromuscular and muscular diseases. The proposed neuromuscular circuit model consists of co-cultured primary motoneurons-interneurons and skeletal myotubes using a unique micropatterned cell culture substrate. The key objective of our neuromuscular junction model is to create a powerful and versatile platform for pharmacological development by both industrial and fundamental research groups. This will be achieved by i) preserving cellular compartmentalization, ii) keeping functional integrity, and iii) ensuring adaptability to different genetic models. Toward the success of our overall goal, the project brings together the necessary expertise in motoneuron cell biology and electrophysiology, as well as micropatterning technology dedicated to cell based assays with industrial purpose.