In Vivo Interrogation of Spinal Mechanosensory Circuits.
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-positive interneurons facilitates both mechanosensory and itch-related behavior, while reversible chemogenetic inhibition of these neurons suppresses mechanosensation. These results extend recent findings regarding the 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.
Department of Electrical Engineering, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
Amelia J
AJ
Christensen
Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
Shrivats M
SM
Iyer
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
Amaury
A
François
Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
Saurabh
S
Vyas
Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
Charu
C
Ramakrishnan
Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
Sam
S
Vesuna
Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
Karl
K
Deisseroth
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA; Department of Neurosurgery, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA; Department of Stanford Neurosciences Institute, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA. Electronic address: gs25@stanford.edu.
Grégory
G
Scherrer
Department of Bioengineering, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA; Department of Mechanical Engineering, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA. Electronic address: delp@stanford.edu.
Scott L
SL
Delp
D000818:Animals; D005260:Female; D006632:Histamine; D007395:Interneurons / Q000502:physiology; D008027:Light; D040542:Mechanotransduction, Cellular; D008810:Mice, Inbred C57BL; D055100:Optical Fibers; D062308:Optogenetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011537:Pruritus / Q000473:pathology / Q000503:physiopathology; D013004:Somatostatin / Q000378:metabolism; D013116:Spinal Cord / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; D013004:Somatostatin; D006632:Histamine
itch; nociception; optogenetics; somatostatin; spinal cord; touch