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Simultaneous voltammetric detection of glucose and lactate fluctuations in rat striatum evoked by electrical stimulation of the midbrain

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Abstract

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.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

We would like to thank Samantha K. Smith, Gregory S. McCarty, Erica M. Cullison, Brian M. Horman, Heather B. Patisaul, and Nathan W. Burnham for equipment, technical assistance, and helpful discussion. Lastly, we would like to thank Pinnacle Technology Inc. for helpful discussion.

Funding

This work was funded by the National Institute of Health (R43MH119870).

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Authors and Affiliations

  1. Department of Chemistry, College of Sciences, North Carolina State University, Raleigh, NC, 27695-8204, USA

    Alexandra G. Forderhase, Hannah C. Styers, Christie A. Lee & Leslie A. Sombers

  2. Comparative Medicine Institute, North Carolina State University, Raleigh, NC, 27695-8204, USA

    Leslie A. Sombers

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  1. Alexandra G. Forderhase
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  2. Hannah C. Styers
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Correspondence to Leslie A. Sombers.

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L.A. Sombers is working with Pinnacle Technologies, Inc., to commercialize these probes through a grant funded by the National Institutes of Health (R43MH119870). The other authors declare no conflict of interest.

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All animal procedures followed Institutional Animal Care and Use Committee (IACUC) and North Carolina State University protocols.

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Forderhase, A.G., Styers, H.C., Lee, C.A. et al. Simultaneous voltammetric detection of glucose and lactate fluctuations in rat striatum evoked by electrical stimulation of the midbrain. Anal Bioanal Chem 412, 6611–6624 (2020). https://doi.org/10.1007/s00216-020-02797-0

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  • DOI: https://doi.org/10.1007/s00216-020-02797-0

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