Metabolic interactions between axons and Schwann cells of the mouse sciatic nerve

The overall aim of the project is to investigate the metabolic interactions between Schwann cells and axons of the peripheral nervous system using the mouse sciatic nerve. A large amount of research has already been conducted into the metabolic interactions between glial cells, mainly astrocytes, and axons of the central nervous system, however evidence is emerging with regards to such interactions between Schwann cells, the glial cells, and axons of the peripheral nervous system. Schwann cells myelinate a population of axons of the sciatic nerve known as A fibres and provide such axons with glycogen derived lactate during times of low/absent glucose supply (Brown et al 2012) as well as fructose derived lactate (Rich & Brown 2018). The nonmyelinated C fibres on the other hand do not benefit from Schwann cell metabolic substrate supply.

Based on research conducted in central nervous system tissue potassium (K+), in addition to others, has been suggested as the metabolic signal passed from axons to glial cells (Choi et al 2012). It has long been thought that astrocytes are selectively permeable to K+ resulting in their membrane potential and changes in it being described as Nernstian (Kuffler et al 1966; Orkand et al 1966). K+ is released from all axons during the repolarisation phase of the action potential thus the K+ specific nature of astrocytes makes them ideal sensors of neuronal activity and subsequent energy demands. However, this K+ membrane potential relationship may not be as perfect as first thought, with a recent suggestion that astrocytes are heterogenous and can be grouped into 2 distinct populations based on their membrane potential (Bolton et al 2006). The selectively permeable nature or not of Schwann cells is yet to be confirmed thus this project aims to obtain reproducible Schwann cell membrane potentials via sharp microelectrodes and determine whether changes in membrane potential can be predicted by the Nernst equation. The project will also focus on the relationship between lactate and K+ using lactate biosensors and K+ sensitive microelectrodes.