Mechanism

The mechanisms of sleep are studied primarily in mammals. Most mammals, especially the model organisms in which sleep studies (cats, rodents, non-human primates, and humans) display primarily bihemispheric sleep patterns. Even these mechanisms of bihemispheric sleep are not fully understood; because of this, the mechanisms of unihemispheric sleep are even more poorly understood. However, critical analysis of bihemispheric sleep studies, as well as some studies of unihemispheric mechanisms in non-classical oganisms, have yielded some insight in to the mechanims of unihemispheric slow-wave sleep (USWS).

Unihemispheric sleep is not controlled by exogenous environmental signals acquired by the eye, because blinded chickens still display USWS (20). It has been argued that auditory cues might control USWS activity; however, ducks can transition between bihemispheric and unihemispheric sleep modes without any aural stimulation (22). It is thus likely that the control of USWS behavior is endogenous. Because the locus of control is inside the animal, the brain has been isolated as the most likely candidate.

 

Brainstem Control of Slow-Wave Sleep

The mammalian arousal (from sleep-to-wake) system utilizes many diverse brain structures. Crucial in initiating arousal is the locus coeruleous (LC) (Figure 1), which contains noradrenergic (NA) neurons that arouse cortical circuits and can drive the sleep-to-wake transition. While many structures are implicated in the arousal of the cortex of from sleep to a waking state, only a few are known to be involved in maintaining the lower activity cortical rhythms of SWS. Specific neurons in the basal forebrain, brainstem, and hypothalamus are all more active during SWS than other sleep or waking states. These neurons release the neurotransmitter gamma-aminobutyric acid (GABA), a typically inhibitory transmitter. The SWS-specific neurons of the basal forebrain extend to both the cortex and back to the brainstem; in this way they could dampen cortical activity during SWS, act as a feedback mechanism to modulate SWS-specific firing neurons in the brainstem, and inhibit the arousal inducing neurons of the LC and other arousing structures of the brainstem. It is clear that the brainstem plays a role in sleep state transitions as well as maintaining sleep and arousal states, including SWS (12).

Figure 1. A human brain showing the position of the locus coeruleus, which is located in the brainstem. From reference 35.

 

Many of the elements involved in sleep regulation are similar in avian and mammalian brains. Relevant to SWS, it has been shown that the stimulation of 2 basal forebrain nuclei of the pigeon brain induces SWS (3).

With the view that the brainstem is involved in the maintenance and control of SWS, Michel (1972) investigated the role of brainstem in SWS in cats (16). After a sagittal transection of the lower brainstem, they found that SWS, usually synchronous across the hemispheres, became asynchronous. Their conclusion cannot be limited to specific nuclei of the brainstem, since their transection was broad, but they show that the gross brainstem structures are likely involved in the control of USWS. The role of the LC in USWS has been investigated in other animals (see section on Comparative Studies below).

 

Fighting Endocrinological Control

Melatonin is a hormone common to all living creatures, synthesized in the pineal gland in both birds and mammals. Transitions between sleep and arousal states can be affected by the release of melatonin from the pineal gland, regulated by circadian rhythms to be released only during the dark phase of the animal's photoperiod (8) (Figure 2). Depending on the species, melatonin can induce sleep (diurnal animals) or wakefulness (nocturnal animals). Melatonin is known to be released by the pineal gland of birds that display USWS. Animals that display USWS must have a mechanism for over-riding these global endocrinological signals; this mechanism has not yet been elucidated.

Figure 2. Melatonin profiles from six individual mice maintained on a 12 hour light/12 hour dark cycle. Grey shading indicates the dark period. From reference 11.

 

Hemispheric Connectivity and Assymetry

Another challenge to the induction of USWS that these brains must overcome is the connection of the hemishperes. Many mammalian brains contain a large structure called the corpus callosum (CC). This structure is made up of bundled neuronal fibers that extend from one hemisphere to the other, providing a functional connectivity between the two sides of the brain. This functional connectivity may present a problem in the separation of the large-scale activity of the hemispheres that is observed during USWS.

It has been theorized that animals that show USWS have either lost or did not evolve the robust connectivity of the CC in order to maintain USWS behavior. In fact, it has been noted that cetaceans have an unusually small CC (33). For example, despite having cerebral hemispheres five times larger than humans, the corpus callosum of killer whales (Orcinus orca) is the same size as in humans. Additionally, birds lack a corpus callosum (Figure 3) and have only small interhemispheric connections (23).

 

Insights from Comparative Studies

One approach to the continued investigation of USWS mechanisms has been comparative studies, investigating the anatomical differences between brains of animals who show USWS and those who don't.

It has been observed that the posterior commissure of mammals utilizing USWS was larger and showed a greater decussation (a crossing in the shape of an X) of ascending fibers from the locus coeruleus in the brainstem than in those mammals lacking USWS. This result may be promising because the noradrenergic neurons of the locus coeruleus are known to be involved in maintaining vigilance and cortical activation. What is even more interesting is that elephants also have this type of posterior commissure, and given recent phylogenetic evidence showing that manatees and elephants share a common aquatic ancestry, it is possible that elephants also sleep unihemispherically (23).