PT  - JOURNAL ARTICLE
AU  - Chen, QiLiang
AU  - Roeder, Zachary
AU  - Li, Ming-Hua
AU  - Zhang, YangMiao
AU  - Ingram, Susan L.
AU  - Heinricher, Mary M.
TI  - Optogenetic Evidence for a Direct Circuit Linking Nociceptive Transmission through the Parabrachial Complex with Pain-Modulating Neurons of the Rostral Ventromedial Medulla (RVM)
AID  - 10.1523/ENEURO.0202-17.2017
DP  - 2017 May 01
TA  - eneuro
PG  - ENEURO.0202-17.2017
VI  - 4
IP  - 3
4099  - http://www.eneuro.org/content/4/3/ENEURO.0202-17.2017.short
4100  - http://www.eneuro.org/content/4/3/ENEURO.0202-17.2017.full
SO  - eNeuro2017 May 01; 4
AB  - The parabrachial complex (PB) is a functionally and anatomically complex structure involved in a range of homeostatic and sensory functions, including nociceptive transmission. There is also evidence that PB can engage descending pain-modulating systems, the best characterized of which is the rostral ventromedial medulla (RVM). Two distinct classes of RVM neurons, “ON-cells” and “OFF-cells,” exert net pronociceptive and anti-nociceptive effects, respectively. PB was recently shown to be a relay of nociceptive information to RVM ON- and OFF-cells. The present experiments used optogenetic methods in a lightly anesthetized rat and an adult RVM slice to determine whether there are direct, functionally relevant inputs to RVM pain-modulating neurons from PB. Whole-cell patch-clamp recordings demonstrated that PB conveys direct glutamatergic and GABAergic inputs to RVM neurons. Consistent with this, in vivo recording showed that nociceptive-evoked responses of ON- and OFF-cells were suppressed by optogenetic inactivation of archaerhodopsin (ArchT)-expressing PB terminals in RVM, demonstrating that a net inhibitory input to OFF-cells and net excitatory input to ON-cells are engaged by acute noxious stimulation. Further, the majority of ON- and OFF-cells responded to optogenetic activation of channelrhodopsin (ChR2)-expressing terminals in the RVM, confirming a direct PB influence on RVM pain-modulating neurons. These data show that a direct connection from the PB to the RVM conveys nociceptive information to the pain-modulating neurons of RVM under basal conditions. They also reveal additional inputs from PB with the capacity to activate both classes of RVM pain-modulating neurons and the potential to be recruited under different physiological and pathophysiological conditions.