Journal ArticleDOI
Temporally precise in vivo control of intracellular signalling
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TLDR
The development of a versatile family of genetically encoded optical tools 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.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.read more
Citations
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Optogenetics in neural systems.
TL;DR: A primer on the application of optogenetics in neuroscience is provided, focusing on the single-component tools and highlighting important problems, challenges, and technical considerations.
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The Development and Application of Optogenetics
TL;DR: The development of currently available single-component optogenetic tools is outlined and the application of various optogenetics tools in diverse model organisms is summarized.
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Plasticity during stroke recovery: from synapse to behaviour.
Timothy H. Murphy,Dale Corbett +1 more
TL;DR: Evidence from animal models suggests that a time-limited window of neuroplasticity opens following a stroke, during which the greatest gains in recovery occur, and how to optimally engage and modify surviving neuronal networks is studied.
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Multimodal fast optical interrogation of neural circuitry
Feng Zhang,Liping Wang,Martin Brauner,Jana F. Liewald,Kenneth Kay,Natalie Watzke,Phillip G. Wood,Ernst Bamberg,Georg Nagel,Alexander Gottschalk,Karl Deisseroth +10 more
TL;DR: In this paper, an archaeal light-driven chloride pump (NpHR) was developed for temporally precise optical inhibition of neural activity, allowing either knockout of single action potentials, or sustained blockade of spiking.
Journal ArticleDOI
Natural Neural Projection Dynamics Underlying Social Behavior
Lisa A. Gunaydin,Logan Grosenick,Joel Finkelstein,Isaac Kauvar,Lief E. Fenno,Avishek Adhikari,Stephan Lammel,Julie J. Mirzabekov,Raag D. Airan,Kelly A. Zalocusky,Kay M. Tye,Polina Anikeeva,Robert C. Malenka,Karl Deisseroth,Karl Deisseroth +14 more
TL;DR: Fiber photometry was developed and applied to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior and captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics.
References
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Journal ArticleDOI
NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory
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TL;DR: This paper showed that the classical models of G-protein coupling and activation of second-messenger-generating enzymes do not fully explain seven-transmembrane receptors' remarkably diverse biological actions.
Journal ArticleDOI
Multimodal fast optical interrogation of neural circuitry
Feng Zhang,Liping Wang,Martin Brauner,Jana F. Liewald,Kenneth Kay,Natalie Watzke,Phillip G. Wood,Ernst Bamberg,Ernst Bamberg,Georg Nagel,Alexander Gottschalk,Karl Deisseroth +11 more
TL;DR: An archaeal light-driven chloride pump from Natronomonas pharaonis is identified and developed for temporally precise optical inhibition of neural activity and forms a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.
Journal Article
Multimodal fast optical interrogation of neural circuitry
Feng Zhang,Liping Wang,Martin Brauner,Jana F. Liewald,Kenneth Kay,Natalie Watzke,Phillip G. Wood,Ernst Bamberg,Georg Nagel,Alexander Gottschalk,Karl Deisseroth +10 more
TL;DR: In this paper, an archaeal light-driven chloride pump (NpHR) was developed for temporally precise optical inhibition of neural activity, allowing either knockout of single action potentials, or sustained blockade of spiking.