Temporally precise in vivo control of intracellular signalling.

Full Abstract

In the study of complex mammalian behaviours, technological limitations have prevented spatiotemporally precise control over intracellular signalling processes. Here we report the development of a versatile family of genetically encoded optical tools ('optoXRs') that leverage common structure-function relationships among G-protein-coupled receptors (GPCRs) to recruit and control, with high spatiotemporal precision, receptor-initiated biochemical signalling pathways. In particular, we have developed and characterized two optoXRs that selectively recruit distinct, targeted signalling pathways in response to light. The two optoXRs exerted opposing effects on spike firing in nucleus accumbens in vivo, and precisely timed optoXR photostimulation in nucleus accumbens by itself sufficed to drive conditioned place preference in freely moving mice. The optoXR approach allows testing of hypotheses regarding the causal impact of biochemical signalling in behaving mammals, in a targetable and temporally precise manner.

Author information

Author/s: Airan, Raag D (RD); Thompson, Kimberly R (KR); Fenno, Lief E (LE); Bernstein, Hannah (H); Deisseroth, Karl (K);

Affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Nature (Nature), published in England. (Language: eng)

Reference: 2009-Apr; vol 458 (issue 7241) : pp 1025-9

Dates: Created 2009/04/27; Completed 2009/06/10;

PMID: 19295515, status: MEDLINE (last retrieved date: 6/10/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

Comments and Corrections

CommentIn: Nature. 2009 Apr 23;458(7241):980-1. (PMID: 19396134)

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals
Cattle
Cell Line
Cricetinae
Cyclic AMP Response Element-Binding Protein - metabolism
Genetic Engineering
Humans
Intracellular Space - metabolism; radiation effects
Mice
Nucleus Accumbens - cytology; physiology; radiation effects

Nucleus Accumbens - cytology; physiology; radiation effects
Receptors, Adrenergic, alpha-1 - genetics; metabolism
Receptors, Adrenergic, beta-2 - genetics; metabolism
Receptors, G-Protein-Coupled - genetics; metabolism
Recombinant Fusion Proteins - genetics; metabolism
Reward
Rhodopsin - genetics; metabolism
Signal Transduction - radiation effects
Structure-Activity Relationship
Time Factors

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Cyclic AMP Response Element-Binding Protein (0) ; Receptors, Adrenergic, alpha-1 (0) ; Receptors, Adrenergic, beta-2 (0) ; Receptors, G-Protein-Coupled (0) ; Recombinant Fusion Proteins (0) ; adrenergic receptor alpha(1a) (0) ; Rhodopsin (9009-81-8)

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