Rapid assessment of in vivo cholinergic transmission by amperometric detection of changes in extracellular choline levels
Abstract
Conventional microdialysis methods for measuring acetylcholine (ACh) efflux do not provide sufficient temporal resolution to relate cholinergic transmission to individual stimuli or behavioral responses, or sufficient spatial resolution to investigate heterogeneities in such regulation within a brain region. In an effort to overcome these constraints, we investigated a ceramic‐based microelectrode array designed to measure amperometrically rapid changes in extracellular choline as a marker for cholinergic transmission in the frontoparietal cortex of anesthetized rats. These microelectrodes exhibited detection limits of 300 n m for choline and selectivity (> 100 : 1) of choline over interferents such as ascorbic acid. Intracortical pressure ejections of choline (20 m m, 66–400 nL) and ACh (10 and 100 m m, 200 nL) dose‐dependently increased choline‐related signals that were cleared to background levels within 10 s. ACh, but not choline‐induced signals, were significantly attenuated by co‐ejection of the acetylcholinesterase inhibitor neostigmine (Neo; 100 m m). Pressure ejections of drugs known to increase cortical ACh efflux, potassium (KCl; 70 m m, 66, 200 nL) and scopolamine (Scop; 10 m m, 200 nL), also markedly increased extracellular choline signals, which again were inhibited by Neo. Scop‐induced choline signals were also found to be tetrodotoxin‐sensitive. Collectively, these findings suggest that drug‐induced increases in current measured with these microelectrode arrays reflect the oxidation of choline that is neuronally derived from the release and subsequent hydrolysis of ACh. Choline signals assessed using enzyme‐selective microelectrode arrays may represent a rapid, sensitive and spatially discrete measure of cholinergic transmission.
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Amperometric measurement using enzyme-coated microelectrodes allows monitoring ACh release at a sub-second resolution.
“The use of enzyme-coated microelectrodes for the amperometric measurement allows monitoring ACh release at a sub-second resolution and thus permits the demonstration of changes in ACh release in association with specific task events or behavioral responses (for evidence indicating the validity of this method see Burmeister et al, 2000; Parikh et al, 2004; Giuliano et al, 2008).”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Parikh et al, 2004
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Self-citation
- Authors
- Parikh, V., Pomerleau, F., Huettl, P., Gerhardt, G. A., Sarter, M., & Bruno, J. P.
- Affiliations
- The Ohio State University (US)
- University of Kentucky (US)
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2004-09
- Volume
- 20
- Issue
- 6
- Pages
- 1545-1554
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W1972854589
- Cited by
- 117
- References
- 53
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 6 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 10 · 2016: 6 · 2015: 9 · 2014: 10 · 2013: 6 · 2012: 6
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH063114, R01MH057436, MH 057436, MH01072, MH 063114, K02MH001072)
- National Institute of Neurological Disorders and Stroke (NS37026, R01NS037026)
- Topics
- Physical Sciences › Engineering › Electrical and Electronic Engineering › Electrochemical sensors and biosensors
- Physical Sciences › Chemistry › Electrochemistry › Electrochemical Analysis and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Keywords
- cholinergic neurotransmission, acetylcholine efflux, amperometric detection, choline oxidation, neostigmine, scopolamine, tetrodotoxin sensitivity, frontoparietal cortex
- MeSH terms
- Acetylcholine, Animals, Brain Chemistry, Cerebral Cortex, Choline, Cholinesterase Inhibitors, Dose-Response Relationship, Drug, Drug Interactions, Electrochemistry, Extracellular Space, Male, Microelectrodes, Neostigmine, Potassium Chloride, Rats, Inbred F344, Scopolamine, Stimulation, Chemical, Time Factors, Microdialysis, Muscarinic Antagonists, Rats
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