VRG receive input from the inspiratory neurons of the DRG
as well as the respiratory rhythm generator and, in turn, have
input to the inspiratory motor neurons. The lower part of the
VRG also contains expiratory neurons that appear to be most
important when large increases in ventilation are required (for
example, during strenuous exercise). During active expira-
tion, motor nerves activated by the expiratory output from the
VRG cause the expiratory muscles to contract. This helps to
move air out of the lungs rather than depending only on the
passive expiration that occurs during quiet breathing.
During quiet breathing, the respiratory rhythm generator
activates inspiratory neurons in the VRG that depolarize the
inspiratory spinal motor nerves, causing the inspiratory muscles
to contract. When the inspiratory motor nerves stop ﬁ ring, the
inspiratory muscles relax, allowing passive expiration. There
are complex interactions within the VRG; for example, inspi-
ratory and expiratory neurons in the medulla show reciprocal
inhibition. Thus, during increases in breathing, the inspiratory
and expiratory motor nerves and muscles are not activated at
the same time, but, rather, alternate in function.
The medullary inspiratory neurons receive a rich synaptic
input from neurons in various areas of the pons, the part of the
brainstem just above the medulla. This input ﬁ ne-tunes the out-
put of the medullary inspiratory neurons and may help termi-
nate inspiration by inhibiting them. It is likely that an area of the
lower pons called the
is the major source of
this output, whereas an area of the upper pons called the
modulates the activity of the apneustic center.
The pneumotaxic center, also known as the
helps to smooth the transition between inspiration
and expiration. The respiratory nerves in the medulla and pons
also receive synaptic input from higher centers of the brain such
that the pattern of respiration is controlled voluntarily during
speaking, diving, and even with emotions and pain.
Another cutoff signal for inspiration comes from
monary stretch receptors,
which lie in the airway smooth
muscle layer and are activated by a large lung inﬂ ation. Action
potentials in the afferent nerve ﬁ bers from the stretch recep-
tors travel to the brain and inhibit the activity of the med-
ullary inspiratory neurons. This is called the
Thus, feedback from the lungs helps to terminate inspi-
ration by inhibiting inspiratory nerves in the DRG. However,
this reﬂ ex plays a role in setting respiratory rhythm only under
conditions of very large tidal volumes, as in strenuous exercise.
The arterial chemoreceptors described next also have impor-
tant input to the respiratory control centers such that the rate
and depth of respiration can be increased when the levels of
arterial oxygen decrease, or when arterial carbon dioxide or
hydrogen ion concentration increases.
A ﬁ nal point about the medullary inspiratory neurons
are that they are quite sensitive to inhibition by drugs such as
barbiturates and morphine. Death from an overdose of these
drugs is often due directly to a cessation of ventilation.
Control of Ventilation by
Respiratory rate and tidal volume are not ﬁ xed but can be
increased or decreased over a wide range. For simplicity, we
will describe the control of ventilation without discussing
whether rate or depth makes the greater contribution to the
There are many inputs to the medullary inspiratory neu-
rons, but the most important for the automatic control of ven-
tilation at rest come from peripheral (arterial) chemoreceptors
and central chemoreceptors.
located high in the
neck at the bifurcation of the common carotid arteries and in
the thorax on the arch of the aorta (
), are called
respectively. In both
locations they are quite close to, but distinct from, the arte-
rial baroreceptors and are in intimate contact with the arterial
blood. The carotid bodies in particular are strategically located
to monitor oxygen supply to the brain. The peripheral che-
moreceptors are composed of specialized receptor cells stimu-
lated mainly by a decrease in the arterial
and an increase
in the arterial H
). These cells
communicate synaptically with neuron terminals from which
afferent nerve ﬁ bers pass to the brainstem. There they provide
excitatory synaptic input to the medullary inspiratory neurons.
The carotid body input is the predominant peripheral chemo-
receptor involved in the control of respiration.
Common carotid artery
Location of the carotid and aortic bodies. Note that each carotid
body is quite close to a carotid sinus, the major arterial baroreceptor.
Both right and left common carotid bifurcations contain a carotid
sinus and a carotid body.