Ganong's Review of Medical Physiology, 23rd Edition

238
SECTION III
Central & Peripheral Neurophysiology

involved in control of the sleep–wake cycles,
preoptic neu-
rons
in the hypothalamus release
GABA
and
posterior hypo-
thalamic 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), wake-
fulness 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 con-
tributes 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 neu-
rons, 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 AND THE

SLEEP–WAKE STATE

In addition to the previously described neurochemical mech-

anisms 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 en-

capsulated 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 invo-

lute before puberty and small concretions of calcium phos-

phate and carbonate

(pineal sand)

appear in the tissue.

Because the concretions are radiopaque, the pineal is often vis-

ible on x-ray films of the skull in adults. Displacement of a cal-

cified 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

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.)

Inhibition

Retinohypothalamic

tract

Suprachiasmatic nucleus

(the "biological clock")

Superior cervical

ganglion

Sympathetic

neurons

Pineal

gland

Stimulation

CH 3 O

H

C

H

H

C

H

H

N

O

C

N

H

CH 3

Melatonin

Day Night