Details

Autor(en) / Beteiligte

• Santos, Ricardo M
• Sirota, Anton

Titel

Phasic oxygen dynamics confounds fast choline-sensitive biosensor signals in the brain of behaving rodents

Ist Teil von

• eLife, 2021-02, Vol.10

Ort / Verlag

England: eLife Science Publications, Ltd

Erscheinungsjahr

2021

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Cholinergic fast time-scale modulation of cortical physiology is critical for cognition, but direct local measurement of neuromodulators in vivo is challenging. Choline oxidase (ChOx)-based electrochemical biosensors have been used to capture fast cholinergic signals in behaving animals. However, these transients might be biased by local field potential and O -evoked enzymatic responses. Using a novel Tetrode-based Amperometric ChOx (TACO) sensor, we performed highly sensitive and selective simultaneous measurement of ChOx activity (COA) and O . In vitro and in vivo experiments, supported by mathematical modeling, revealed that non-steady-state enzyme responses to O give rise to phasic COA dynamics. This mechanism accounts for most of COA transients in the hippocampus, including those following locomotion bouts and sharp-wave/ripples. Our results suggest that it is unfeasible to probe phasic cholinergic signals under most behavioral paradigms with current ChOx biosensors. This confound is generalizable to any oxidase-based biosensor, entailing rigorous controls and new biosensor designs.