Chemogenetics—A Transformational and Translational Platform

English, Justin G.; Roth, Bryan L.

doi:10.1001/jamaneurol.2015.1921

Cited by 37 publications

(31 citation statements)

References 65 publications

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“…We therefore tested whether transient inhibition of somatostatin+ interneuron activity would confirm model predictions, recapitulating aspects of previously observed behavior (Duan et al, 2014). Two major strategies have been used to reversibly inhibit neural circuits—optogenetic inhibition (Adamantidis et al, 2015; Boyden, 2015; Deisseroth, 2015) and the use of chemogenetic Gi-coupled DREADDs (Armbruster et al, 2007; English and Roth, 2015; Iyer et al, 2016; Urban and Roth, 2015). Here, we adopted a chemogenetic strategy for two reasons: 1) lamina II neurons exhibit large rostro-caudal patterns of activation in response to primary afferent input (Nishida et al, 2014), and we were concerned that the narrow field of illumination provided by an implanted fiber optic ferrule would not be sufficient to drive behavior and 2) optogenetic inhibition typically requires high intensity constant light, which, given the high density of TRPV1 expression in nociceptor terminals in the dorsal spinal cord, poses a significant heating-related activation confound.…”

Section: Resultsmentioning

confidence: 99%

In Vivo Interrogation of Spinal Mechanosensory Circuits

et al. 2016

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Summary Spinal dorsal horn circuits receive, process, and transmit somatosensory information. To understand how specific components of these circuits contribute to behavior, it is critical to be able to directly modulate their activity in unanesthetized in vivo conditions. Here, we develop experimental tools that enable optogenetic control of spinal circuitry in freely moving mice using commonly available materials. We use these tools to examine mechanosensory processing in the spinal cord, and observe that optogenetic activation of somatostatin+ interneurons facilitates both mechanosensory and itch-related behavior, while reversible chemogenetic inhibition of these neurons suppresses mechanosensation. These results extend recent findings regarding processing of mechanosensory information in the spinal cord and indicate the potential for activity-induced release of the somatostatin neuropeptide to affect processing of itch. The spinal implant approach we describe here is likely to enable a wide range of studies to elucidate spinal circuits underlying pain, touch, itch, and movement.

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Section: Resultsmentioning

confidence: 99%

In Vivo Interrogation of Spinal Mechanosensory Circuits

et al. 2016

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“…As shown in Table 1 (for recent reviews, see Sternson and Roth, 2014;Urban and Roth, 2015; English and Roth, 2015), there now exist many GPCR-based chemogenetic tools. These include first- (“Alelle-specific GPCRs”; Strader et al, 1991), second-(RASSLs and “Engineered GPCRs”; Coward et al, 1998; Westkaemper et al, 1999), and third-generation (DREADDs; Armbruster and Roth, 2005; Armbruster et al, 2007) platforms.…”

Section: Current Dreaddsmentioning

confidence: 99%

“…Many therapeutic applications of DREADD-based therapeutics have been suggested, including diabetes (Jain et al, 2013), metabolic disorders (Li et al, 2013), Parkinson’s Disease (Dell’Anno et al, 2014), psychostimulant (Ferguson et al, 2011) and ethanol (Pleil et al, 2015) abuse, depression (Urban et al, 2015), post-traumatic stress disorder (Zhu et al, 2014), intractable seizures (Kätzel et al, 2014), inflammatory disorders (Park et al, 2014), autism (Peñagarikano et al, 2015), and many other disorders (English and Roth, 2015). DREADDs have been successfully expressed in nonhuman primates without apparent toxicity, and an exciting new report demonstrates that CNO-DREADDs can modulate circuitry, electrophysiology, and behavior in nonhuman primates (Eldridge et al, 2016).…”

Section: Areas For Enhancement Of Dreadd Technologiesmentioning

confidence: 99%

DREADDs for Neuroscientists

Roth

2016

Neuron

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To understand brain function, it is essential that we discover how cellular signaling specifies normal and pathological brain function. In this regard, chemogenetic technologies represent valuable platforms for manipulating neuronal and non-neuronal signal transduction in a cell-type-specific fashion in freely moving animals. Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-based chemogenetic tools are now commonly used by neuroscientists to identify the circuitry and cellular signals that specify behavior, perceptions, emotions, innate drives, and motor functions in species ranging from flies to nonhuman primates. Here I provide a primer on DREADDs highlighting key technical and conceptual considerations and identify challenges for chemogenetics going forward.

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“…Development of chemogenetics as well as optogenetics has been provided innovative knowledge in the field of neuroscience 1,2 . In recent research projects, these techniques have been widely used to understand the linkage between central nervous activity and diverse behaviours.…”

Section: Introductionmentioning

confidence: 99%

Activation of endogenous arginine vasopressin neurons inhibit food intake: by using a novel transgenic rat line with DREADDs system

Yoshimura

Nishimura

et al. 2017

Sci Rep

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Various studies contributed to discover novel mechanisms of central arginine vasopressin (AVP) system responsible for the behaviour albeit endogenous vasopressin activation. We established a novel transgenic rat line which expresses both human muscarinic acetylcholine receptors (hM3Dq), of which ligand is clozapine-N-oxide (CNO), and mCherry fluorescence specifically in AVP neurons. The mCherry neurons that indicate the expression of the hM3Dq gene were observed in the suprachiasmatic (SCN), supraoptic (SON), and paraventricular nuclei (PVN). hM3Dq-mCherry fluorescence was localized mainly in the membrane of the neurons. The mCherry neurons were co-localized with AVP-like immunoreactive (LI) neurons, but not with oxytocin-LI neurons. The induction of Fos, which is the indicator for neuronal activity, was observed in approximately 90% of the AVP-LI neurons in the SON and PVN 90 min after intraperitoneal (i.p.) administration of CNO. Plasma AVP was significantly increased and food intake, water intake, and urine volume were significantly attenuated after i.p. administration of CNO. Although the detailed mechanism has unveiled, we demonstrated, for the first time, that activation of endogenous AVP neurons decreased food intake. This novel transgenic rat line may provide a revolutionary insight into the neuronal mechanism regarding central AVP system responsible for various kind of behaviours.

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Chemogenetics—A Transformational and Translational Platform

Cited by 37 publications

References 65 publications

In Vivo Interrogation of Spinal Mechanosensory Circuits

In Vivo Interrogation of Spinal Mechanosensory Circuits

DREADDs for Neuroscientists

Activation of endogenous arginine vasopressin neurons inhibit food intake: by using a novel transgenic rat line with DREADDs system

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