title: Inhibitory Interneurons That Express GFP in the PrP-GFP Mouse Spinal Cord Are Morphologically Heterogeneous, Innervated by Several Classes of Primary Afferent and Include Lamina I Projection Neurons among Their Postsynaptic Targets.
abstract: The superficial dorsal horn of the spinal cord contains numerous inhibitory interneurons, which regulate the transmission of information perceived as touch, pain, or itch. Despite the importance of these cells, our understanding of their roles in the neuronal circuitry is limited by the difficulty in identifying functional populations. One group that has been identified and characterized consists of cells in the mouse that express green fluorescent protein (GFP) under control of the prion protein (PrP) promoter. Previous reports suggested that PrP-GFP cells belonged to a single morphological class (central cells), received inputs exclusively from unmyelinated primary afferents, and had axons that remained in lamina II. However, we recently reported that the PrP-GFP cells expressed neuronal nitric oxide synthase (nNOS) and/or galanin, and it has been shown that nNOS-expressing cells are more diverse in their morphology and synaptic connections. We therefore used a combined electrophysiological, pharmacological, and anatomical approach to reexamine the PrP-GFP cells. We provide evidence that they are morphologically diverse (corresponding to "unclassified" cells) and receive synaptic input from a variety of primary afferents, with convergence onto individual cells. We also show that their axons project into adjacent laminae and that they target putative projection neurons in lamina I. This indicates that the neuronal circuitry involving PrP-GFP cells is more complex than previously recognized, and suggests that they are likely to have several distinct roles in regulating the flow of somatosensory information through the dorsal horn.
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Ganley
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Noboru
authors.initials: N
authors.lastname: Iwagaki
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Patricia
authors.initials: P
authors.lastname: del Rio
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Najma
authors.initials: N
authors.lastname: Baseer
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Allen C
authors.identifier: http://orcid.org/0000-0002-6339-2801
authors.initials: AC
authors.lastname: Dickie
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Kieran A
authors.initials: KA
authors.lastname: Boyle
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Erika
authors.initials: E
authors.lastname: Polgár
authors.affiliation: Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan, and.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Abraira
authors.affiliation: Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Amanda
authors.initials: A
authors.lastname: Zimmerman
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom, andrew.todd@glasgow.ac.uk john.riddell@glasgow.ac.uk.
authors.forename: John S
authors.initials: JS
authors.lastname: Riddell
authors.affiliation: Spinal Cord Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, United Kingdom, andrew.todd@glasgow.ac.uk john.riddell@glasgow.ac.uk.
authors.forename: Andrew J
authors.identifier: http://orcid.org/0000-0002-3007-6749
authors.initials: AJ
authors.lastname: Todd
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D055592:Biophysical Phenomena / Q000187:drug effects / Q000235:genetics; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D018689:Sensory System Agents / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology*
chemical_list: D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D016761:Oncogene Proteins v-fos; D011328:Prions; D018040:Receptors, Neurokinin-1; D018689:Sensory System Agents; D049452:Green Fluorescent Proteins; D052248:Nitric Oxide Synthase Type I; D002211:Capsaicin
keywords: confocal microscopy; galanin; neuronal nitric oxide synthase; whole-cell recording