Final Report Summary - NEURO-GLIAL SYNAPSES (Neuronal Activity: Targets for Stimulating Myelin Formation and Repair in the Brain) The scientific objective of the project was to investigate the influence of neuronal activity and AMPA-type glutamate receptors (AMPAR) on the development of oligodendrocytes and the formation of myelin. The work would also develop methodologies for exploring the morphological development of oligodendrocytes in fixed and living cells, and for assessing the impact of activity on oligodendrocyte calcium signalling and morphology. Findings arising from these studies described new data indicating important roles for neuronal activity and AMPAR in the development of oligodendrocytes and the formation of CNS myelin. During the project new findings obtained from dissociated cell cultures were published demonstrating a role for NNMDA type glutamate receptors (NMDAR) in myelination. Consequently, additional studies were performed to examine NMDAR functions in our slice culture system. These experiments did not confirm a role for NMDAR in oligodendrocyte development. The results have been submitted for publication in Glia and revisions are currently being prepared. The project also lead to the successful development of a set of probes suitable for the real-time analysis of activity-dependent oligodendrocyte development in brain slice cultures. These include a neuron-targeting vector delivering Channel Rhodopsin 2, and a set of glial cell targeting vectors to deliver genetically encoded calcium indicators (both cytoplasmic and membrane tethered) to resolve the physiological response of oligodendrocytes following optogenetic stimulation of neighbouring axons. In addition a neuron-targeting red wavelength calcium vector has been generated to enable simultaneous axon / glial calcium imaging experiments. Studies involving these tools are now underway and promise to deliver novel findings on the nature of activity-dependent axon-oligodendrocyte interactions. These developments represent valuable tools for axon-glial research that offer new opportunities to advance the state-of-the-art in the myelin biology field. During the project Dr Fulton moved his CIG project to the University of Birmingham where he took up a new position as a Birmingham Fellow. This competitively awarded tenure-tracked fellowship provides 5-years of protected research time (limited teaching load) and is equivalent to an academic appointment at the lecturer grade. The fellowship delivered significant support for Dr Fulton to start his lab, and also provided funds to employ a postdoctoral fellow for 2 years. His new appointment provides all of the research independence and institutional research support expected of a regular lecturer appointment. He has the freedom to supervise his own PhD students, and apply for his own independent project grants. Overall, the combination of career security and excellent institutional support provided by this position indicate that Dr Fulton’s career integration is proceeding well and he has very good prospects for a stable research career at the University of Birmingham. Throughout the project Dr Fulton has engaged in a number of dissemination and training and supervisory roles that have enabled effective transfer of his knowledge and expertise to the Universities of Warwick, Birmingham, and the regional neuroscience community. These include hosting a live-imaging workshop, mentoring research students, the delivery of undergraduate lectures on myelin biology, and the training of researchers on confocal imaging and the analysis of oligodendrocyte development.
