446 Neuroanatomy: Draw It to Know It
Wakefulness Circuitry
Before the center for sleep was proven, the center for
wakefulness was discovered. In the 1940s and 1950s
neurophysiologists Giuseppe Moruzzi and H. W.
Magoun performed a series of EEG studies to prove the
existence of the wakefulness center. Th ey described an
active arousal generator in the brainstem reticular for-
mation, coined the ascending reticular activating system,
which was shown to directly and indirectly activate the
cerebral cortex by way of diff use projection fi bers that
projected directly to the cortex and also indirectly to the
cortex through the thalamus. Over the past several
decades, discovery of the specifi c brainstem, hypotha-
lamic, thalamic, and basal forebrain cell populations
responsible for the arousal system has elaborated and
shaped our understanding of wakefulness anatomy.
Numerous neurotransmitters and neuronal populations
within the brainstem, hypothalamus, thalamus, and basal
forebrain have been discovered, some of which we will
specifi cally indicate here.
In the corner of the diagram, for reference, draw a
mid-sagittal view of a brain. Next, in the center of the
page, draw an expanded view of the basal forebrain,
hypothalamus, and brainstem. To begin our process of
labeling the wake-promoting cells, indicate the latero-
dorsal tegmental and pedunculopontine nuclei in the
lower midbrain and upper pons and show that they are
cholinergic. Next, we will draw the upper brainstem
monoaminergic nuclei. In the posterior pons, draw the
locus coeruleus and label it as noradrenergic (the largest
concentration of locus coeruleus neurons lies within
the pons); in the anterior midbrain, group the substantia
nigra and ventral tegmental area together and show that
they are dopaminergic; and fi nally, in the central upper
pons and midbrain, draw the dorsal group of raphe
nuclei and indicate that they are serotinergic. Note that
the locus coeruleus, substantia nigra, and raphe nuclei
are drawn in greater detail in Chapter 9. Next, move to
the hypothalamus. Draw the tuberomammillary nucleus
in the hypothalamus; it is the sole source of histamine in
the brain and it is important for wakefulness. Now,
include the cholinergic basal forebrain nuclei in the
ventral surface of the frontal lobe; they are important to
wakefulness. Finally, consider that in Drawings 20-3 and
20-4, we showed that the intralaminar thalamic nuclei
also play an important role in the arousal system.
As a pharmacologic corollary to the list of neuro-
transmitters involved in wakefulness, consider that
amphetamines are adrenergic reuptake inhibitors and
are stimulatory — they increase the amount of circulat-
ing monoamines; consider that anti histamines, such as
diphenhydramine (Benadryl), cause drowsiness, as do
anti cholinergic agents; and consider that tricyclic anti-
depressants can be especially sedating because they
oft en have both anti cholinergic and anti histaminergic
properties.^13