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PLoS One. 2014 Apr 7;9(4):e94080. doi: 10.1371/journal.pone.0094080. eCollection 2014.

Central connectivity of transient receptor potential melastatin 8-expressing axons in the brain stem and spinal dorsal horn.

Author information

1
Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, Korea.
2
Neurobiology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California, United States of America.

Abstract

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.

PMID:
24710558
PMCID:
PMC3977991
DOI:
10.1371/journal.pone.0094080
[Indexed for MEDLINE]
Free PMC Article

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