Dataset Information

GPCR-Based Dopamine Sensors-A Detailed Guide to Inform Sensor Choice for In vivo Imaging.

ABSTRACT: Understanding how dopamine (DA) encodes behavior depends on technologies that can reliably monitor DA release in freely-behaving animals. Recently, red and green genetically encoded sensors for DA (dLight, GRAB-DA) were developed and now provide the ability to track release dynamics at a subsecond resolution, with submicromolar affinity and high molecular specificity. Combined with rapid developments in in vivo imaging, these sensors have the potential to transform the field of DA sensing and DA-based drug discovery. When implementing these tools in the laboratory, it is important to consider there is not a 'one-size-fits-all' sensor. Sensor properties, most importantly their affinity and dynamic range, must be carefully chosen to match local DA levels. Molecular specificity, sensor kinetics, spectral properties, brightness, sensor scaffold and pharmacology can further influence sensor choice depending on the experimental question. In this review, we use DA as an example; we briefly summarize old and new techniques to monitor DA release, including DA biosensors. We then outline a map of DA heterogeneity across the brain and provide a guide for optimal sensor choice and implementation based on local DA levels and other experimental parameters. Altogether this review should act as a tool to guide DA sensor choice for end-users.

SUBMITTER: Labouesse MA

PROVIDER: S-EPMC7672611 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

GPCR-Based Dopamine Sensors-A Detailed Guide to Inform Sensor Choice for In vivo Imaging.

Labouesse Marie A MA Cola Reto B RB Patriarchi Tommaso T

International journal of molecular sciences 20201028 21

Understanding how dopamine (DA) encodes behavior depends on technologies that can reliably monitor DA release in freely-behaving animals. Recently, red and green genetically encoded sensors for DA (dLight, GRAB-DA) were developed and now provide the ability to track release dynamics at a subsecond resolution, with submicromolar affinity and high molecular specificity. Combined with rapid developments in in vivo imaging, these sensors have the potential to transform the field of DA sensing and DA ...[more]

PMID: 33126757

Similar Datasets

Project description:Animal studies support the role of the dopamine D3 receptor (DRD3) in alcohol reinforcement or liking. Sustained voluntary alcohol drinking in rats has been associated with an upregulation of striatal DRD3 gene expression and selective blockade of DRD3 reduces ethanol preference, consumption, and cue-induced reinstatement. In vivo measurement of DRD3 in the living human brain has not been possible until recently owing to a lack of suitable tools. In this study, DRD3 status was assessed for the first time in human alcohol addiction. Brain DRD3 availability was compared between 16 male abstinent alcohol-dependent patients and 13 healthy non-dependent age-matched males using the DRD3-preferring agonist positron emission tomography (PET) radioligand [(11)C]PHNO with and without blockade with a selective DRD3 antagonist (GSK598809 60 mg p.o.). In striatal regions of interest, where the [(11)C]PHNO PET signal represents primarily DRD2 binding, no differences were seen in [(11)C]PHNO binding between the groups at baseline. However, baseline [(11)C]PHNO binding was higher in alcohol-dependent patients in hypothalamus (VT: 16.5 ± 4 vs 13.7 ± 2.9, p = 0.040), a region in which the [(11)C]PHNO signal almost entirely reflects DRD3 availability. The reductions in regional receptor binding (VT) following a single oral dose of GSK598809 (60 mg) were consistent with those observed in previous studies across all regions. There were no differences in regional changes in VT following DRD3 blockade between the two groups, indicating that the regional fractions of DRD3 are similar in the two groups, and the increased [(11)C]PHNO binding in the hypothalamus in alcohol-dependent patients is explained by elevated DRD3 in this group. Although we found no difference between alcohol-dependent patients and controls in striatal DRD3 levels, increased DRD3 binding in the hypothalamus of alcohol-dependent patients was observed. This may be relevant to the development of future therapeutic strategies to treat alcohol abuse.

Dataset Information

GPCR-Based Dopamine Sensors-A Detailed Guide to Inform Sensor Choice for In vivo Imaging.

Publications

GPCR-Based Dopamine Sensors-A Detailed Guide to Inform Sensor Choice for In vivo Imaging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets