PT  - JOURNAL ARTICLE
AU  - Rika Moriya
AU  - Mitsuko Kanamaru
AU  - Naoki Ookuma
AU  - Akira Yoshikawa
AU  - Kenji F. Tanaka
AU  - Satoshi Hokari
AU  - Yasuyoshi Ohshima
AU  - Masahiko Izumizaki
TI  - Optogenetic silencing of selected serotonin neurons in the control of CO<sub>2</sub>-induced arousal
AID  - 10.1183/13993003.congress-2016.PA2299
DP  - 2016 Sep 01
TA  - European Respiratory Journal
PG  - PA2299
VI  - 48
IP  - suppl 60
4099  - http://erj.ersjournals.com/content/48/suppl_60/PA2299.short
4100  - http://erj.ersjournals.com/content/48/suppl_60/PA2299.full
SO  - Eur Respir J2016 Sep 01; 48
AB  - Serotonin (5-HT) neurons in both medullary and midbrain raphe nuclei sense changes in the partial pressure of arterial CO2. Arousal from sleep in response to hypercapnia (i.e., CO2-induced arousal) may be important in diseases such as obstructive sleep apnea syndrome (OSA) and sudden infant death syndrome (SIDS). 5-HT neurons are reportedly necessary for CO2-induced arousal, although the underlying mechanism is not understood. Here, we examined how central 5-HT neurons contribute to sleep/wake regulation during hypercapnia by using optogenetic methods to selectively stimulate or suppress specific serotonergic neuronal populations. We used transgenic mice (provided by the RIKEN Bio Resource Center) in which central 5-HT neurons were genetically targeted by archaerhodopsin, a green light-driven neuronal silencer, or by channelrhodopsin-2, a blue light-driven neuronal activator. An optical fiber (diameter, 0.5 mm) was inserted just above the dorsal raphe (DR) or the raphe obscurus (RO), and an EEG/EMG telemeter was implanted subcutaneously in each mouse. After 10 days of recovery, the mice were placed in a whole-body plethysmograph (EMKA Technologies), and the optical fibers were illuminated by a telemetric system (Teleopto, Bio Research Center) during CO2 inhalation. All vigilance state classifications assigned by analyzing software (Sleep Sign, KISSEI COMTEC) were confirmed visually and corrected if necessary. The present study tested our hypothesis that DR and RO 5-HT neurons play a crucial role in CO2-induced arousal. Further investigation of the underlying serotonergic mechanisms may lead to development of pharmacotherapies that reduce morbidity and mortality from SIDS and OSA.