Ganong's Review of Medical Physiology, 23rd Edition

626
SECTION VII
Respiratory Physiology

the reciprocal inhibition is a small amount of activity in
phrenic axons for a short period after inspiration. The func-
tion of this post-inspiratory output appears to be to brake the
lung’s elastic recoil and make respiration smooth.

MEDULLARY SYSTEMS

The main components of the

respiratory control pattern gen-

erator

responsible for automatic respiration are located in the

medulla. Rhythmic respiration is initiated by a small group of

synaptically coupled pacemaker cells in the

pre-Bötzinger com-

plex

(pre-BÖTC) on either side of the medulla between the nu-

cleus ambiguus and the lateral reticular nucleus (Figure 37–1).

These neurons discharge rhythmically, and they produce rhyth-

mic discharges in phrenic motor neurons that are abolished by

sections between the pre-Bötzinger complex and these motor

neurons. They also contact the hypoglossal nuclei, and the

tongue is involved in the regulation of airway resistance.

Neurons in the pre-Bötzinger complex discharge rhythmi-

cally in brain slice preparations in vitro, and if the slices

become hypoxic, discharge changes to one associated with

gasping. Addition of cadmium to the slices causes occa-

sional sigh-like discharge patterns. There are NK1 receptors

and

μ

-opioid receptors on these neurons, and, in vivo, sub-

stance P stimulates and opioids inhibit respiration. Depres-

sion of respiration is a side effect that limits the use of opioids

in the treatment of pain. However, it is now known that 5HT

4

receptors are present in the pre-Bötzinger complex and treat-

ment with 5HT

4

agonists blocks the inhibitory effect of opiates

on respiration in experimental animals, without inhibiting

their analgesic effect.

In addition, dorsal and ventral groups of respiratory neu-

rons are present in the medulla (Figure 37–2). However,

lesions of these neurons do not abolish respiratory activity,

and they apparently project to the pre-Bötzinger pacemaker

neurons.

FIGURE 37–1
Pacemaker cells in the pre-Bötzinger complex
(pre-BÖTC). Top:
Anatomical diagram of the pre-BÖTC from a neona-
tal rat

. Bottom:
Sample rhythmic discharge tracing of neurons in the
pre-BÖTC complex from a brain slice of a neonatal rat. IO, inferior olive;
LRN, lateral reticular nucleus; NA, nucleus ambiguus; XII, nucleus of
12th cranial nerve; 5SP, spinal nucleus of trigeminal nerve.
(Modified
from Feldman JC, Gray PA: Sighs and gasps in a dish. Nat Neurosci 2000;3:531.)

−60 mV

20 mV

5 s

5SP

XII

NA

IO

LRN Pre-BOTC

••

FIGURE 37–2
Respiratory neurons in the brain stem.
Dorsal view of brain stem; cerebellum removed. The effects of various lesions and
brain stem transections are shown; the spirometer tracings at the right indicate the depth and rate of breathing. If a lesion is introduced at D,
breathing ceases. The effects of higher transections, with and without vagus nerves transection, are shown (see text for details). DRG, dorsal group
of respiratory neurons; VRG, ventral group of respiratory neurons; NPBL, nucleus parabrachialis (pneumotaxic center); 4th vent, fourth ventricle;
IC, inferior colliculus; CP, middle cerebellar peduncle. The roman numerals identify cranial nerves.
(Modified from Mitchell RA, Berger A: State of the art:
Review of neural regulation of respiration. Am Rev Respir Dis 1975;111:206.)

4th

vent

NPBL

CP

IC

VRG

DRG

A

B

C

D

IX

X

XI

XII

Vagi intact Vagi cut