RT Journal Article
SR Electronic
T1 Identification and Characterization of a Sleep-Active Cell Group in the Rostral Medullary Brainstem
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 17970
OP 17976
DO 10.1523/JNEUROSCI.0620-12.2012
VO 32
IS 50
A1 Christelle Anaclet
A1 Jian-Sheng Lin
A1 Ramalingam Vetrivelan
A1 Martina Krenzer
A1 Linh Vong
A1 Patrick M. Fuller
A1 Jun Lu
YR 2012
UL http://www.jneurosci.org/content/32/50/17970.abstract
AB Early transection and stimulation studies suggested the existence of sleep-promoting circuitry in the medullary brainstem, yet the location and identity of the neurons comprising this putative hypnogenic circuitry remains unresolved. In the present study, we sought to uncover the location and identity of medullary neurons that might contribute to the regulation of sleep. Here we show the following in rats: (1) a delimited node of medullary neurons located lateral and dorsal to the facial nerve—a region we termed the parafacial zone (PZ)—project to the wake-promoting medial parabrachial nucleus; (2) PZ neurons express c-Fos after sleep but not after wakefulness and hence are sleep active; and (3) cell-body-specific lesions of the PZ result in large and sustained increases (50%) in daily wakefulness at the expense of slow-wave sleep (SWS). Using transgenic reporter mice [vesicular GABA/glycine transporter (Vgat)–GFP], we then show that >50% of PZ sleep-active neurons are inhibitory (GABAergic/glycinergic, VGAT-positive) in nature. Finally, we used a Cre-expressing adeno-associated viral vector and conditional Vgatlox/lox mice to selectively and genetically disrupt GABA/glycinergic neurotransmission from PZ neurons. Disruption of PZ GABAergic/glycinergic neurotransmission resulted in sustained increases (40%) in daily wakefulness at the expense of both SWS and rapid eye movement sleep. These results together reveal the location and neurochemical identity of a delimited node of sleep-active neurons within the rostral medullary brainstem.