Original Research ARTICLE

Front. Neurosci., 11 February 2014 | http://dx.doi.org/10.3389/fnins.2014.00020

Orexin A and orexin receptor 1 axonal traffic in dorsal roots at the CNS/PNS interface

Damien Colas1,2*, Annalisa Manca2, Jean-Dominique Delcroix2 and Philippe Mourrain3,4*
  • 1Department of Biology, Stanford University, Stanford, CA, USA
  • 2Laboratory of Neurodegeneration and Axon Dynamics, European Brain Research Institute, Rome, Italy
  • 3Department of Psychiatry and Behavioral Sciences, Center for Sleep Sciences, Beckman Center, Stanford University, Stanford, CA, USA
  • 4INSERM 1024, Ecole Normale Supérieure, Paris, France

Hypothalamic orexin/hypocretin neurons send long axonal projections through the dorsal spinal cord in lamina I–II of the dorsal horn (DH) at the interface with the peripheral nervous system (PNS). We show that in the DH OXA fibers colocalize with substance P (SP) positive afferents of dorsal root ganglia (DRG) neurons known to mediate sensory processing. Further, OR1 is expressed in p75NTR and SP positive DRG neurons, suggesting a potential signaling pathway between orexin and DRG neurons. Interestingly, DRG sensory neurons have a distinctive bifurcating axon where one branch innervates the periphery and the other one the spinal cord (pseudo-unipolar neurons), allowing for potential functional coupling of distinct targets. We observe that OR1 is transported selectively from DRG toward the spinal cord, while OXA is accumulated retrogradely toward the DRG. We hence report a rare situation of asymmetrical neuropeptide receptor distribution between axons projected by a single neuron. These molecular and cellular data are consistent with the role of OXA/OR1 in sensory processing, including DRG neuronal modulation, and support the potential existence of an OX/HCRT circuit between CNS and PNS.

Keywords: orexin, hypocretin, receptor 1, dorsal root ganglia, axonal transport, nociception, substance P

Citation: Colas D, Manca A, Delcroix J-D and Mourrain P (2014) Orexin A and orexin receptor 1 axonal traffic in dorsal roots at the CNS/PNS interface. Front. Neurosci. 8:20. doi: 10.3389/fnins.2014.00020

Received: 09 September 2013; Accepted: 23 January 2014;
Published online: 11 February 2014.

Edited by:

Christopher J. Winrow, Merck, USA

Reviewed by:

Gabriella Gobbi, McGill University, Canada
Daya S. Gupta, Camden County College, USA
Kyle Baumbauer, University of Pittsburgh Medical School, USA
Chloe Alexandre, Beth Israel Deaconess Medical Center, USA

Copyright © 2014 Colas, Manca, Delcroix and Mourrain. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Damien Colas, Department of Biology, Stanford University, 371 Serra Mall, Stanford, CA 94305, USA e-mail: colas@stanford.edu;
Philippe Mourrain, Center for Sleep Sciences, Beckman Center, Stanford University, 279 Campus Drive, Room B201, Stanford, CA 94305, USA e-mail: mourrain@stanford.edu