Astrocytes supply glycogen-derived lactate to central nervous system axons during simulated aglycaemia, a feature shared with Schwann cells that myelinate sciatic nerve A fibres, a peripheral nerve (Brown et al., 2003, 2005, 2012). However, only astrocytes, to date, are known to supply axons with glycogen-derived lactate during increased neuronal activity (Brown et al., 2003, 2005). We report on-going investigations into the putative supply of glycogen-derived lactate during high frequency stimulation (HFS) in peripheral nerve, providing further insight into a possible universal theory of axon-glia metabolic interactions in the central and peripheral nervous system. All procedures were carried out in accordance with the Animals (Scientific Procedures) Act 1986 under appropriate authority of establishment, project and personal licenses. Adult male CD-1 mice were killed by cervical dislocation and decapitated. Sciatic nerves were dissected, placed in a perfusion chamber, superfused with aerated aCSF containing 10mM glucose. The compound action potential (CAP) was evoked with supra-maximal stimuli at a baseline frequency of 1Hz, with its amplitude monitored as a measure of conduction. HFS was defined as 100Hz. The maintenance of A fibre conduction during HFS was assessed in the presence of 10mM (n=9) or 30mM (n=9) glucose, revealing an energy demand versus supply relationship. Lactate uptake into axons is prevented by 200µM cinnamate; its addition to 30mM glucose during HFS had no effect (n=5), but when supplied with 10mM glucose conduction failed (n=4), suggesting a requirement for lactate under normoglycemic conditions. Since the source of this lactate is unclear, nerves were exposed to HFS for increasing durations in 10mM or 30mM glucose before removal of substrate supply. In substrate free conditions glycogen is the sole source of energy therefore glycogen content determines latency to failure. Increasing the duration of exposure to 10mM glucose and HFS reduced the latency to failure in subsequent substrate free conditions (58 24.9mins after 2hrs (n=4), 34.7 6.5mins after 4hrs (n=5) and 38.3 11.5mins after 6hrs (n=4) compared with 94.3 15.1mins after baseline incubation in 10mM glucose at 1Hz (n=14)), implying a role of glycogen during both HFS and normoglycemic conditions. In contrast, latency to failure after extended exposure to 30mM glucose and HFS was increased (101.7 35.1mins after 2hrs (n=4) and 132.8 18.0mins after 4hrs (n=4) compared with 94.3 15.1mins after baseline incubation (n=14)), suggesting glucose is supplied surplus to demand; excess glucose stored as glycogen in Schwann cells. During increased neuronal activity, sciatic nerve A fibres require increased energy substrate in order to maintain conduction, as expected. This can be achieved by increased supply of glucose; alternatively, Schwann cell lactate, potentially glycogen derived, may provide support.