LAUSR

Glucose and lactate provide energy for cellular function in the brain and serve as an important carbon source in the synthesis of a variety of biomolecules. Thus, there is a critical need to quantitatively monitor these molecules in situ on a time scale commensurate with neuronal function. In this work, carbon-fiber microbiosensors were coupled with fast-scan cyclic voltammetry to monitor glucose and lactate fluctuations at a discrete site within rat striatum upon electrical stimulation of the midbrain projection to the region. Systematic variation of stimulation parameters revealed the distinct dynamics by which glucose and lactate responded to the metabolic demand of synaptic function. Immediately upon stimulation, extracellular glucose and lactate availability rapidly increased. If stimulation was sufficiently intense, concentrations then immediately fell below baseline in response to incurred metabolic demand. The dynamics were dependent on stimulation frequency, such that more robust fluctuations were observed when the same number of pulses was delivered at a higher frequency. The rates at which glucose was supplied to, and depleted from, the local recording region were dependent on stimulation intensity, and glucose dynamics led those of lactate in response to the most substantial stimulations. Glucose fluctuated over a larger concentration range than lactate as stimulation duration increased, and glucose fell further from baseline concentrations. These real-time measurements provide an unprecedented direct comparison of glucose and lactate dynamics in response to metabolic demand elicited by neuronal activation. Graphical abstract