Abstract

A method for simultaneous electrochemical detection of brain tissue PO2 (PtO2) and pH changes together with neuronal activity using a modified form of fast cyclic voltammetry with carbon fiber electrodes is described. This technique has been developed for in vivo applications and recordings from discrete brain nuclei in experimental animals. The small size of the carbon fiber electrode (⌀7 μm, length <100 μm) ensures minimal disruption of the brain tissue and allows recordings from small brain areas. Sample rate (up to 4 Hz) is sufficient to resolve rapid changes in PtO2 and pH that follow changes in neuronal activity and metabolism. Rapid switching between current and voltage recordings allows combined electrochemical detection and monitoring of extracellular action potentials. For simultaneous electrochemical detection of PtO2 and pH, two consecutive trapezoidal voltage ramps are applied with double differential-subtraction of the background current. This enables changes in current caused by protons and oxygen to be detected separately with minimal interference between the two. The profile of PtO2 changes evoked by increases in local neuronal activity recorded using the described technique was very similar to that of blood-oxygen-level-dependent responses recorded using fMRI. This voltammetric technique can be combined with fMRI and brain vessel imaging to study the metabolic mechanisms underlying neurovascular coupling response with much greater spatial and temporal resolution than is currently possible.

Highlights

  • The method described here has been developed to study the mech­ anisms underlying the neurovascular coupling response (Hosford and Gourine, 2018)

  • Changes in brain tissue PO2, PCO2 and pH correlate with changes in neuronal activity and could potentially contribute to neurovascular coupling via a metabolic feed-back mechanism, as was originally proposed by Roy and Sher­ rington, (1890)

  • We describe a novel Fast-cyclic voltammetry (FCV)-based technique that enables simultaneous recordings of key vari­ ables representing the metabolic state of the brain: brain tissue PO2, pH and neuronal activity

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Summary

Introduction

The method described here has been developed to study the mech­ anisms underlying the neurovascular coupling response (Hosford and Gourine, 2018). The mechanisms of neurovascular coupling contribute to accurate matching of brain oxygen and glucose supply with demand. Despite intense experi­ mental scrutiny over the last two decades, the mechanisms underlying the neurovascular coupling response are not fully understood and are surrounded by controversies (Hosford and Gourine, 2018). Changes in brain tissue PO2, PCO2 and pH correlate with changes in neuronal activity and could potentially contribute to neurovascular coupling via a metabolic feed-back mechanism, as was originally proposed by Roy and Sher­ rington, (1890)

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