RT Journal Article
SR Electronic
T1 Identification of Sympathetic Premotor Neurons in Medullary Raphe Regions Mediating Fever and Other Thermoregulatory Functions
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5370
OP 5380
DO 10.1523/JNEUROSCI.1219-04.2004
VO 24
IS 23
A1 Kazuhiro Nakamura
A1 Kiyoshi Matsumura
A1 Thomas Hübschle
A1 Yoshiko Nakamura
A1 Hiroyuki Hioki
A1 Fumino Fujiyama
A1 Zsolt Boldogköi
A1 Matthias König
A1 Heinz-Jürgen Thiel
A1 Rüdiger Gerstberger
A1 Shigeo Kobayashi
A1 Takeshi Kaneko
YR 2004
UL http://www.jneurosci.org/content/24/23/5370.abstract
AB Sympathetic premotor neurons directly control sympathetic preganglionic neurons (SPNs) in the intermediolateral cell column (IML) of the thoracic spinal cord, and many of these premotor neurons are localized in the medulla oblongata. The rostral ventrolateral medulla contains premotor neurons controlling the cardiovascular conditions, whereas rostral medullary raphe regions are a candidate source of sympathetic premotor neurons for thermoregulatory functions. Here, we show that these medullary raphe regions contain putative glutamatergic neurons and that these neurons directly control thermoregulatory SPNs. Neurons expressing vesicular glutamate transporter 3 (VGLUT3) were distributed in the rat medullary raphe regions, including the raphe magnus and rostral raphe pallidus nuclei, and mostly lacked serotonin immunoreactivity. These VGLUT3-positive neurons expressed Fos in response to cold exposure or to central administration of prostaglandin E2, a pyrogenic mediator. Transneuronal retrograde labeling after inoculation of pseudorabies virus into the interscapular brown adipose tissue (BAT) or the tail indicated that those VGLUT3-expressing medullary raphe neurons innervated these thermoregulatory effector organs multisynaptically through SPNs of specific thoracic segments, and microinjection of glutamate into the IML of the BAT-controlling segments produced BAT thermogenesis. An anterograde tracing study further showed a direct projection of those VGLUT3-expressing medullary raphe neurons to the dendrites of SPNs. Furthermore, intra-IML application of glutamate receptor antagonists blocked BAT thermogenesis triggered by disinhibition of the medullary raphe regions. The present results suggest that VGLUT3-expressing neurons in the medullary raphe regions constitute excitatory neurons that could be categorized as a novel group of sympathetic premotor neurons for thermoregulatory functions, including fever.