Introduction
The master circadian pacemaker, the suprachiasmatic nucleus (SCN),
controls circadian timing of sleep and wakefulness. SCN ablations in
rodents, despite completely abolishing circadian rhythms of sleep-wake
behavior, do not alter total sleep or wake amounts (Ibuka & Kawamura,
1975) . However, lesions of the SCN in squirrel monkeys eliminate
circadian rhythms of sleep-wake behavior but also reduce total wake time
by 15% (Edgar et al. , 1993) , suggesting that the SCN may
promote wake in rodents. Delineating the circadian independent pathways
by which the SCN promotes arousal will enrich the mechanisms of SCN
control of arousal. The paraventricular nucleus of hypothalamic (PVH)
regulates autonomic function (Leibowitz et al. , 1981) and food
intake (Atasoy et al. , 2012; Garfield et al. , 2015) , it
receives direct inputs from the SCN (Ono et al. , 2020) , and
mediates circadian control of the SCN on pineal melatonin and
corticosterone release (Klein et al., 1983; Jones et al. ,
2021). It has been reported that corticotropin-releasing factor (CRF)
neurons in the PVH mediate wakefulness via the SCN projection (Onoet al. , 2020; Chen et al. , 2021). As the PVH projects to
the parabrachial nucleus (PB), a key brainstem arousal center (Qiuet al. , 2016; Lv et al. , 2023), the PVH may mediates
arousal via the PB.
The retrochiasmatic area (RCA), an area situated immediately ventral to
the third ventricle, behind the SCN and in front of the arcuate nucleus
receives massive SCN inputs and is involved in control of the circadian
amplitude of N-acetylserotonin and melatonin by the pineal gland (Camposet al. , 2014) . Both SCN and RCA are critical for pulsatile
luteinizing hormone (LH) secretion (Arendash & Gallo, 1979). We
hypothesize that the SCN, RCA, PVH and PB constitute an arousal network.
We used designer Receptors Exclusively Activated by Designer Drugs
(DREADDs) to examine the effects of activation of the RCA, SCN, PVH and
PVH-PB pathway on wake behavior.