Central connectivity of transient receptor potential melastatin 8-expressing axons in the brain stem and spinal dorsal horn.
Transient receptor potential melastatin 8 (TRPM8) ion channels mediate the detection of noxious and innocuous cold and are expressed by primary sensory neurons, but little is known about the processing of the TRPM8-mediated cold information within the trigeminal sensory nuclei (TSN) and the spinal dorsal horn (DH). To address this issue, we characterized TRPM8-positive (+) neurons in the trigeminal ganglion and investigated the distribution of TRPM8+ axons and terminals, and their synaptic organization in the TSN and in the DH using light and electron microscopic immunohistochemistry in transgenic mice expressing a genetically encoded axonal tracer in TRPM8+ neurons. TRPM8 was expressed in a fraction of small myelinated primary afferent fibers (23.7%) and unmyelinated fibers (76.3%), suggesting that TRPM8-mediated cold is conveyed via C and Aδ afferents. TRPM8+ axons were observed in all TSN, but at different densities in the dorsal and ventral areas of the rostral TSN, which dominantly receive sensory afferents from intra- and peri-oral structures and from the face, respectively. While synaptic boutons arising from Aδ and non-peptidergic C afferents usually receive many axoaxonic contacts and form complex synaptic arrangements, TRPM8+ boutons arising from afferents of the same classes of fibers showed a unique synaptic connectivity; simple synapses with one or two dendrites and sparse axoaxonic contacts. These findings suggest that TRPM8-mediated cold is conveyed via a specific subset of C and Aδ afferent neurons and is processed in a unique manner and differently in the TSN and DH.
Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Yun Sook
YS
Kim
Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Jun Hong
JH
Park
Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Su Jung
SJ
Choi
Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Jin Young
JY
Bae
Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Dong Kuk
DK
Ahn
Neurobiology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.
David D
DD
McKemy
Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
Yong Chul
YC
Bae
D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000378:metabolism*; D014278:Trigeminal Nuclei / Q000378:metabolism*
D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse