442 Neuroanatomy: Draw It to Know It
Sleep Neurocircuitry ( Advanced )
Here, we will learn the neurocircuitry of sleep: we will
learn the anatomic location of the sleep center, the phys-
iolog y of the thalamocortical circuits, and the pathway
for the generation of REM sleep. Indicate that the area
for non-REM sleep induction lies within the anterior
hypothalamus, specifi cally in the ventrolateral preoptic
area and the median preoptic nucleus. Baron Constantin
von Economo fi rst hypothesized that this area was the
sleep induction center when in 1916–17 he studied the
clinical–pathologic correlations of patients who had
died from encephalitis lethargica (aka von Economo’s
encephalitis). Th e parkinsonian and oculomotor mani-
festations found in patients with that disorder led him
to postulate that the sleep induction center lies within
the anterior hypothalamus and the area for wakefulness
lies, roughly, within the posterior hypothalamus/upper
brainstem, and over the next several decades, he was
proven, to a large extent, correct (see Figure 25-1 ).^1
Now, let’s shift our discussion to the physiolog y of
sleep: specifi cally, we will show how the thalamocortical
networks generate sleep electroencephalographic (EEG)
patterns — sleep spindles and slow-wave sleep. First, let’s
draw the major cell populations responsible for this net-
work; draw the thalamus and label the GABAergic retic-
ular thalamic neurons, and then draw the T-type calcium
channel thalamocortical neurons. Next, draw the corti-
cal pyramidal cells. Th e reticular thalamic nuclei gate the
fl ow of information between the thalamus and cortex,
and the thalamocortical neurons drive cortical EEG pat-
terns through, at least in part, the low-threshold spike.
To illustrate the physiolog y of the low-threshold
spike, include in our diagram a graph of the membrane
potential of the thalamocortical neurons. Label voltage
on the Y-axis and time on the X-axis. Th en, demarcate
the –65 mV point. Now, show that excitation of the
reticular thalamic nuclei causes GABAergic inhibition
of thalamocortical cells. Th en, indicate that eventually
the thalamocortical membrane hyperpolarizes more
negatively than –65 mV, which causes the T-type calcium
channels to open, which generates a low-threshold spike:
a burst of action potentials. In our drawing, show that
the thalamocortical burst acts both on the reticular thal-
amic cells to facilitate their rhythmic oscillation and also
on the cortical pyramidal neurons, which generate the
EEG patterns observed during sleep. Lastly, show that
aft er the low-threshold spike, there is a refractory period
for the thalamocortical neurons. Indicate that as a
byproduct of the refractory period, there is cessation of
the excitatory thalamocortical inputs to such relay neu-
rons as the lateral geniculate nucleus, which results in
the phenomenon of sensory gating : the process wherein
sensory stimuli that might otherwise wake us from sleep
fail to reach our cerebral cortex.^2 – 6
Now, let’s turn our attention to REM sleep. Note
that no defi nitive model for REM sleep has been con-
fi rmed and our fl ow diagram, here, represents only a
best hypothesis. First, indicate that the putative primary
REM-promoting region lies within the pons, in what is
called the sublaterodorsal nucleus in the rat and the peri-
locus coeruleus in the cat. Indicate that this region excites
the cortex to produce the characteristic EEG pattern of
REM sleep, and also excites a constellation of nuclei
called the supra-olivary medulla to produce muscle
atonia during REM sleep. Now, indicate that during
wakefulness and non-REM sleep, the ventrolateral peri-
aqueductal gray area and the dorsal deep mesencephalic
reticular nucleus tonically inhibit the sublaterodorsal
nucleus/peri-locus coeruleus. Lastly, show that during
REM sleep, the dorsal paragigantocellular nucleus (in
the medulla) and the lateral hypothalamic melanin-
concentrating hormone nuclei suppress the ventrolateral
periaqueductal gray area and dorsal deep mesencephalic
reticular nuclei, which disinhibits the sublaterodorsal
nucleus/peri-locus coeruleus, freeing them to act on the
supra-olivary medulla and cerebral cortex to produce
REM sleep as previously described.^7 – 10