In a recent issue of Journal of Neuroscience, researchers used a well-appreciated technique to determine how the major sleep-wake and circadian regulatory areas respond to whole-brain depletion of serotonin in rats. Serotonin is one of many neurotransmitters that controls daily rhythms of sleep and wakefulness in humans and rodents. While (healthy) human sleep is very consolidated, rodent sleep is often characterized as spontaneous even though there is still a distinctive rhythm of sleep and wake amounts across the light and dark periods of a photocycle. In this study, the researchers used multiunit activity which enables for the sampling of neuronal activity in a live, freely-behaving animal instead of in a dish, which can be done, but is problematic due to deafferentation of input and output pathways to and from the structure of interest. The areas sampled were; 1) the SCN, wherein lies the master circadian pacemaker; 2) the basal forebrain/preoptic area, which regulate recovery from sleep loss; and 3) several higher-order cognitive areas such as the frontal cortex and hippocampus. These images show diurnal rhythms of multiunit activity in each of these areas prior to drug treatment. As you can see, diurnal rhythms of neuronal activity in the SCN compared with the basal forebrain and sleep regulatory areas are anti-phasic.

 

Serotonin depletion was undertaken through a microinjection of TSOI in the respective areas. To ensure that the serotonergic depleting effects of TSOI were not secondary to TSOI depletion of melatonin, C57BL/6J mice were used because these mice don’t produce melatonin anyways. Although the TSOI injection did not affect SCN rhythms of neuronal activity by any means, rhythms in the basal forebrain were severely attenuated, while others were highly variable (either retained or repressed). Further, a reduction in diurnal rhythmicity in the basal forebrain corresponded with more sporadic, less consolidated rhythms of sleep and wake, with an emphasis on changes in NREM sleep cycles and amounts (increased cycling but decrease in duration). Further, there was not a change in sleep-wake rhythms following the injection of alpha-MT which depletes catecholamines (dopamine and epinephrine). There was also an increase in sleep-wake ultrarhythmicity and subsequent loss of neuronal rhythms in the basal forebrain following application of ritaserin which is a 5-HT2 receptor blockade. Overall, this study maps sleep-wake regulatory areas sensitive to serotonergic innervation and lends further credence to serotonergic regulation of daily sleep-wake rhythms.

Miyamoto, H., Nakamaru-Ogiso, E., Hamada, K., & Hensch, T. (2012). Serotonergic Integration of Circadian Clock and Ultradian Sleep-Wake Cycles Journal of Neuroscience, 32 (42), 14794-14803 DOI: 10.1523/JNEUROSCI.0793-12.2012