Interactions between neurons and glial cells underlie the normal development, structure and function of the nervous system. Perturbation of this communication occurs during injury, in acquired or hereditary neuropathic diseases of the central and peripheral nervous systems, and with ageing. However, the specific nature and the physiological significance of neuron-glia interactions remain largely unknown. We propose here the use of a microfluidic co-culture platform to characterize and investigate the role of non-synaptic responses of glial cells following stimulation of neuronal activity. In particular, we will co-culture neurons and glial cells of the peripheral nervous system, and monitor glia-specific changes at the transcriptome- and the secretome-levels, after manipulation of the electrical activity of neurons. We will subsequently interfere with the identified signaling pathways, and study effects on neuronal structure and function. Following this in vitro approach, we expect to identify potential mediators of the axon-glia communication and decipher their role in maintaining the nervous system integrity and function.