Remote Optogenetic Activation and Sensitization of Pain Pathways in Freely Moving Mice

Daou, I.; Tuttle, Alexander H.; Longo, Geraldine; Wieskopf, Jeffrey S.; Bonin, Robert P.; Ase, Ariel R.; Wood, John N.; Koninck, Yves De; Ribeiro‐da‐Silva, Alfredo; Mogil, Jeffrey S.; Séguéla, Philippe

doi:10.1523/jneurosci.2424-13.2013

Cited by 157 publications

(196 citation statements)

References 22 publications

(7 reference statements)

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“…In particular, it was difficult to selectively activate a specific type of heterogeneous population of neurons. The incorporation of optogenetics has provided a better understanding of the complex circuit, showing a robust application in pain research from behavioral [4,11] to cellular levels [3,4,21]. In our present study, by selectively expressing ChR2 on PV neurons, we achieved a realtime gain-of-function for specific neuron types and manipulated GABA release by a light pulse.…”

Section: Discussionmentioning

confidence: 89%

Optoactivation of parvalbumin neurons in the spinal dorsal horn evokes GABA release that is regulated by presynaptic GABAB receptors

Yang

Wang

et al. 2015

Neuroscience Letters

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Section: Discussionmentioning

confidence: 89%

Optoactivation of parvalbumin neurons in the spinal dorsal horn evokes GABA release that is regulated by presynaptic GABAB receptors

Yang

Wang

et al. 2015

Neuroscience Letters

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“…But the ability to combine single-cell electrophysiology with single-cell optical sensing and activation in vivo using novel micro-optrodes will be particularly instrumental to determine the role of specific subpopulation of cells within the intact circuit and in contextual environment 73 . Another example stems from selective optogenetic activation of pathways, which can allow comparison of synaptic plasticity in slices with sensitization at the behavioral level via activation of the exact same input with the same temporal characteristics 74 .…”

Section: The Optical Revolutionmentioning

confidence: 99%

Normal and abnormal coding of somatosensory stimuli causing pain

2014

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Noxious stimuli cause pain and pain arises from noxious stimuli… usually. Exceptions to these apparent truisms are the basis for clinically important problems and provide valuable insight into the neural code for pain. In this Perspective, we will discuss how painful sensations are encoded. We will argue that although primary somatosensory afferents are specialized (i.e. tuned to specific stimulus features), natural stimuli often activate >1 type of afferent. Manipulating co-activation patterns can alter perception, which argues against each type of afferent acting independently (as expected for strictly labeled lines) and suggests instead that signals conveyed by different types of afferents interact. Deciphering the central circuits that mediate those interactions is critical for explaining the generation and modulation of neural signals ultimately perceived as pain. The advent of genetic and optical dissection techniques promise to dramatically accelerate progress towards this goal, which will facilitate the rational design of future pain therapeutics.

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“…In electrophysiological recordings, an approachwell-suited to study synaptic transmission, subpopulations of A- and C-fibres cannot readily be distinguished, unless genetic modifications are introduced [10;47]. Here we employed an optogenetic approach to specifically investigate subpopulations of VGluT3 + sensory fibres.…”

Section: Introductionmentioning

confidence: 99%

Presynaptic inhibition of optogenetically identified VGluT3+ sensory fibres by opioids and baclofen

Honsek

Seal

Sandkühler

2015

Pain

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Distinct subsets of sensory nerve fibres are involved in mediating mechanical and thermal pain hypersensitivity. They may also differentially respond to analgesics. Heat-sensitive C-fibres, for example, are thought to respond to µ-opioid receptor (MOR) activation while mechanoreceptive fibres are supposedly sensitive to δ-opioid receptor (DOR) or GABAB receptor (GABABR) activation. The suggested differential distribution of inhibitory neurotransmitter receptors on different subsets of sensory fibres is, however, heavily debated. We now quantitatively compared the degree of presynaptic inhibition exerted by opioids and the GABABR agonist baclofen on 1) vesicular glutamate transporter subtype 3 positive (VGluT3+) non-nociceptive primary afferent fibres and 2) putative nociceptive C-fibres. To investigate VGluT3+ sensory fibres, we evoked excitatory postsynaptic currents with blue light at the level of the dorsal root ganglion (DRG) in spinal cord slices of mice, expressing channelrhodopsin-2. Putative nociceptive C-fibres were explored in VGluT3-knockout mice via electrical stimulation. The MOR agonist DAMGO strongly inhibited both VGluT3+ and VGluT3− C-fibres innervating lamina I neurons but generally had less influence on fibres innervating lamina II neurons. The DOR agonist SNC80 did not have any pronounced effect on synaptic transmission in any fibre type tested. Baclofen, in striking contrast, powerfully inhibited all fibre populations investigated. In summary, we report optogenetic stimulation of DRG neurons in spinal slices as capable approach for the subtype-selective investigation of primary afferent nerve fibres. Overall, the pharmacological accessibility of different subtypes of sensory fibres considerably overlaps, indicating that MOR, DOR and GABABR expression is not substantially segregated between heat and mechanosensitive fibres.

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Remote Optogenetic Activation and Sensitization of Pain Pathways in Freely Moving Mice

Abstract: We report a novel model in which remote activation of peripheral nociceptive pathways in transgenic mice is achieved optogenetically, without any external noxious stimulus or injury. Taking advantage of a binary genetic approach, we selectively targeted Na v 1.

Cited by 157 publications

References 22 publications

Optoactivation of parvalbumin neurons in the spinal dorsal horn evokes GABA release that is regulated by presynaptic GABAB receptors

Optoactivation of parvalbumin neurons in the spinal dorsal horn evokes GABA release that is regulated by presynaptic GABAB receptors

Normal and abnormal coding of somatosensory stimuli causing pain

Presynaptic inhibition of optogenetically identified VGluT3+ sensory fibres by opioids and baclofen

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