Ganong's Review of Medical Physiology, 23rd Edition

238 SECTION III Central & Peripheral Neurophysiology
Inhibition
Stimulation
Retinohypothalamic
tract
Suprachiasmatic nucleus
(the "biological clock")
CH 3 O
FIGURE 15–11 Secretion of melatonin. Retinohypothalamic fibers synapse in the suprachiasmatic nuclei (SCN), and there are connections
from the SCN to sympathetic preganglionic neurons in the spinal cord that project to the superior cervical ganglion. Postganglionic neurons
project from this ganglion to the pineal gland that secretes melatonin. The cyclic activity of SCN sets up a circadian rhythm for melatonin release.
This rhythm is entrained to light/dark cycles by neurons in the retina. (From Fox SI: Human Physiology. McGraw-Hill, 2008.)
involved in control of the sleep–wake cycles, preoptic neurons
in the hypothalamus release GABA and posterior hypothalamic
neurons release histamine.
One theory regarding the basis for transitions from sleep to
wakefulness involves alternating reciprocal activity of different
groups of RAS neurons. In this model (Figure 15–12), wakefulness
and REM sleep are at opposite extremes. When the
activity of norepinephrine- and serotonin-containing neurons
(locus coeruleus and raphé nuclei) is dominant, there is a
reduced level of activity in acetylcholine-containing neurons
in the pontine reticular formation. This pattern of activity contributes
to the appearance of the awake state. The reverse of
this pattern leads to REM sleep. When there is a more even
balance in the activity of the aminergic and cholinergic neurons,
NREM sleep occurs.
In addition, an increased release of GABA and reduced
release of histamine increase the likelihood of NREM sleep
via deactivation of the thalamus and cortex. Wakefulness
occurs when GABA release is reduced and histamine release
is increased.
Melatonin
H H H O
C C N C CH3
N
H
H H
Sympathetic
neurons
Superior cervical
ganglion
Pineal
gland
MELATONIN AND THE
SLEEP–WAKE STATE
Day Night
In addition to the previously described neurochemical mechanisms
promoting changes in the sleep–wake state, melatonin
release from the richly vascularized pineal gland plays a role
in sleep mechanisms (Figure 15–11). The pineal arises from
the roof of the third ventricle in the diencephalon and is encapsulated
by the meninges. The pineal stroma contains glial
cells and pinealocytes with features suggesting that they have
a secretory function. Like other endocrine glands, it has highly
permeable fenestrated capillaries. In infants, the pineal is large
and the cells tend to be arranged in alveoli. It begins to involute
before puberty and small concretions of calcium phosphate
and carbonate (pineal sand) appear in the tissue.
Because the concretions are radiopaque, the pineal is often visible
on x-ray films of the skull in adults. Displacement of a calcified
pineal from its normal position indicates the presence of
a space-occupying lesion such as a tumor in the brain.
Melatonin and the enzymes responsible for its synthesis from
serotonin by N-acetylation and O-methylation are present in
pineal pinealocytes, and the hormone is secreted by them into
the blood and the cerebrospinal fluid (Figure 15–13). Two