RanvierNodes-WMUnits · Defining the function of nodes of Ranvier as regulatory units of the white matter

The human brain is divided into the grey matter and the white matter (WM). The grey matter includes the synapses which are paramount for processing information, while the WM consists of myelinated axon bundles that conduct information between different brain areas. Brain information processing relies heavily on precise spike timing. This raises questions about the preservation of spike-encoded timing information as it propagates across WM axons, which can extend tens of centimetres before reaching synapses. My research challenges the view that myelinated axons merely serve as electrical conduits in the brain and proposes that the WM contains regulatory units essential for processing information along myelinated axons. I hypothesise that nodes of Ranvier, small unmyelinated gaps along myelinated axons where spikes are generated, function as these regulatory units. My previous findings indicate that nodes of Ranvier play a crucial role in shaping axon excitability and conduction speed, because they can undergo rapid changes in the electrical properties of their membrane and slower changes in their structure. These changes are triggered by variations in neuronal activity and in the calcium activity of astrocytes, whose processes interact closely with nodes. Here, I will combine state-of-the-art microscopy with multiple patch-clamping in mouse and human brain tissue, and computer modelling. I will investigate the properties of nodes of Ranvier underpinning their impulse-regulating functions, focusing on four characteristics that endow them with this ability: their membrane excitability, electrical adaptability, structural adaptability and connections with other cells.By dissecting the functions of nodes of Ranvier in this way, my research aims to deepen our understanding of neural network intricacies, offering insights into fundamental mechanisms of information processing in the brain, and emphasising the importance of the white matter in this processing.