摘要：SummaryIn vivosensing of neurotransmitters has provided valuable insight into both healthy and diseased brain. However, chronically implanted Ag/AgCl reference electrodes suffer from degradationgradation, resulting in errors in the potential at the working electrode. Here, we report a simple, effective way to protectin vivosensing measurements from reference polarization with a replaceable subcutaneously implanted reference. We compared a brain-implanted reference and a subcutaneous reference and observed no difference in impedance or dopamine redox peak separation in an acute preparation. Chronically, peak background potential and dopamine oxidation potential shifts were eliminated for three weeks. Scanning electron microscopy shows changes in surface morphology and composition of chronically implanted Ag/AgCl electrodes, and postmortem histology reveals extensive cell death and gliosis in the surrounding tissue. As accurate reference potentials are critical toin vivoelectrochemistry applications, this simple technique can improve a wide and diverse assortment ofin vivopreparations.Graphical abstractDisplay OmittedHighlights•Chronic reference electrodes in the brain degrade, resulting in inaccurate voltages•Implantation also causes substantial tissue damage and cell death•A replaceable subcutaneous reference enables more accurate chronic measurements•Brain tissue damage is also eliminated with a subcutaneous referenceElectrochemistry experimental methods; Neuroscience; Methodology in biological sciences
