Epidural optogenetics for controlled analgesia

Abstract

BackgroundOptogenetic tools enable cell selective and temporally precise control of neuronal activity; yet, difficulties in delivering sufficient light to the spinal cord of freely behaving animals have hampered the use of spinal optogenetic approaches to produce analgesia. We describe an epidural optic fiber designed for chronic spinal optogenetics that enables the precise delivery of light at multiple wavelengths to the spinal cord dorsal horn and sensory afferents.ResultsThe epidural delivery of light enabled the optogenetic modulation of nociceptive processes at the spinal level. The acute and repeated activation of channelrhodopsin-2 expressing nociceptive afferents produced robust nocifensive behavior and mechanical sensitization in freely behaving mice, respectively. The optogenetic inhibition of GABAergic interneurons in the spinal cord dorsal horn through the activation of archaerhodopsin also produced a transient, but selective induction of mechanical hypersensitivity. Finally, we demonstrate the capacity of optogenetics to produce analgesia in freely behaving mice through the inhibition of nociceptive afferents via archaerhodopsin.ConclusionEpidural optogenetics provides a robust and powerful solution for activation of both excitatory and inhibitory opsins in sensory processing pathways. Our results demonstrate the potential of spinal optogenetics to modulate sensory behavior and produce analgesia in freely behaving animals.

Levels of Cocaine- and Amphetamine-Regulated Transcript in Vagal Afferents in the Mouse Are Unaltered in Response to Metabolic Challenges

“…Na v 1.8-Cre mice crossed with either tdTomato or ChR2 reporter animals have previously been used to label the perikarya and axons of C-fibers, including somatosensory nociceptors (Gautron et al, 2011; Shields et al, 2012; Daou et al, 2013; Bonin et al, 2016). To our knowledge, this is the first study to use Na v 1.8-Cre-ChR2-YFP mice to describe visceral C-fibers.…”

Flexible Near-Field Wireless Optoelectronics as Subdermal Implants for Broad Applications in Optogenetics

“…Optogenetics avoids these complications through the use of photosensitive ion channels or proteins in genetically modified neurons to allow optical stimulation or inhibition of activity in a highly targeted and controlled fashion (Boyden et al, 2005; Deisseroth, 2011; Fenno et al, 2011; Packer et al, 2013; Siuda et al, 2015a, b; Sparta et al, 2012; Toettcher et al, 2011; Yizhar et al, 2011). This methodology is considered as essential for current efforts in neuroscience research largely due to its capabilities for sophisticated functional studies in the central and peripheral nervous systems (Bonin et al, 2015; Boyden et al, 2005; Iyer et al, 2014; Kim et al, 2013; Sparta et al, 2012; Towne et al, 2013). Recent developments in material science and electrical engineering combine this optical control with the use of soft, flexible optoelectronic implants that deliver light directly to regions of interest using ultraminiaturized light emitting diodes (LEDs), powered and controlled wirelessly (Jeong et al, 2015; Kim et al, 2013; McCall et al, 2013; Park et al, 2015a, b).…”

Fully implantable, battery-free wireless optoelectronic devices for spinal optogenetics

“…Unlike the brain, where the skull provides a bony anchor point to stabilize optic fibers or head stages for wired or battery-powered light sources, the spinal cord presents unique engineering challenges. Previous studies involving optogenetic approaches to study spinal circuits have relied on epidural optic fiber implants and tethering via fiber optic cables to laser or light-emitting diode (LED) light sources [4; 6; 8; 25]. Although this approach is valuable, tethered operation impedes movement, which can induce stress leading to altered behaviors.…”