Remote Control of Neuronal Signaling
Open accessAbstract
A significant challenge for neuroscientists is to determine how both electrical and chemical signals affect the activity of cells and circuits and how the nervous system subsequently translates that activity into behavior. Remote, bidirectional manipulation of those signals with high spatiotemporal precision is an ideal approach to addressing that challenge. Neuroscientists have recently developed a diverse set of tools that permit such experimental manipulation with varying degrees of spatial, temporal, and directional control. These tools use light, peptides, and small molecules to primarily activate ion channels and G protein-coupled receptors (GPCRs) that in turn activate or inhibit neuronal firing. By monitoring the electrophysiological, biochemical, and behavioral effects of such activation/inhibition, researchers can better understand the links between brain activity and behavior. Here, we review the tools that are available for this type of experimentation. We describe the development of the tools and highlight exciting in vivo data. We focus primarily on designer GPCRs (receptors activated solely by synthetic ligands, designer receptors exclusively activated by designer drugs) and microbial opsins (e.g., channelrhodopsin-2, halorhodopsin, Volvox carteri channelrhodopsin) but also describe other novel techniques that use orthogonal receptors, caged ligands, allosteric modulators, and other approaches. These tools differ in the direction of their effect (activation/inhibition, hyperpolarization/depolarization), their onset and offset kinetics (milliseconds/minutes/hours), the degree of spatial resolution they afford, and their invasiveness. Although none of these tools is perfect, each has advantages and disadvantages, which we describe, and they are all still works in progress. We conclude with suggestions for improving upon the existing tools.
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Mutated muscarinic DREADD receptors respond exclusively to CNO and are unresponsive to endogenous ligand acetylcholine.
“These mutated muscarinic receptors respond exclusively to clozapine-N-oxide (CNO) and are unresponsive to their endogenous ligand acetylcholine (Armbruster et al., 2007;Rogan and Roth, 2011).”
From Single-cell resolution analysis of the crosstalk between chemogenically activated astrocytes and microglia (2020) · cites this paper as Rogan and Roth, 2011
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“These mutated muscarinic receptors respond exclusively to 60 clozapine-N-oxide (CNO) and are unresponsive to their endogenous ligand acetylcholine 61 (Armbruster et al., 2007; Rogan and Roth, 2011).”
Background
- Authors
- Rogan, S. C., & Roth, B. L.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- ORCID
- Roth, Bryan L.
- Venue
- Pharmacological Reviews
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 63
- Issue
- 2
- Pages
- 291-315
- ISSN
- 0031-6997 (ISSN-L)
- PMC
- PMC3082452
- OpenAlex
- W2103253964
- Cited by
- 339
- References
- 8
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 17 · 2023: 14 · 2022: 15 · 2021: 20 · 2020: 16 · 2019: 29 · 2018: 28 · 2017: 32 · 2016: 41 · 2015: 39 · 2014: 31 · 2013: 30 · 2012: 11
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pharmacological Reviews (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Triangle Community Foundation
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- National Institute of Mental Health (U19MH082441, MH087074, MH082441, R01MH061887, MH061887, F30MH087074)
- National Institute of General Medical Sciences (T32GM008719, GM008719)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- optogenetics, microbial opsins, channelrhodopsin-2, halorhodopsin, DREADD, allosteric modulators, ion channel activation, G protein-coupled receptors, neuronal firing, brain-behavior relationship
- MeSH terms
- Animals, Humans, Ligands, Light, Neurons, Peptides, Designer Drugs, Signal Transduction, Receptors, G-Protein-Coupled, Opsins
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