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Control of breathing: Objectives

• Describe Obstructive Sleep
Apnea (OSA) from a control
of breathing perspective
• List the 3 general features of a
respiratory controller & the
primary components
• Outline the organization of
brain stem respiratory regions
• Brain stem regions:
• Impact of neural sections
in the brain
• Role of medulla, pons
and cortex in breathing
• Name brain stem
structures with
respiratory neurons

Control of breathing: Objectives

• Spinal cord mechanisms

• Identify the brain region of respiration :
responsible for generation of • Name the locations of
rhythmic breathing spinal phrenic
• Describe the role of a motorneurons and the
mammalian rhythm generator muscle they innervate
• Contrast automatic and
ondine... who is she? voluntary respiratory
spinal pathways

Mr. A.L. integrated control of breathing & disease…

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Ryan Chow: 6.5 min to fall asleep

Ryan Chow: never reaches REM sleep

Ryan Chow: VERY long duration of apnea

Ryan Chow: use the PaO2 equation to calculate

Obstructive Sleep Apnea

Central Apnea: Brain fails to generate a breath Ryan Chow: This leads to obstructive Sleep Apnea

Ryan Chow: No air flow, yet there is muscle activity.

Something wrong in the brain

Snoring happens from an exterior perspective Ryan Chow: mails have it worse than females

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Features of Respiratory
Control

Ryan Chow: efferents from brain stem and brain

Ryan Chow: Most likely for the guy that the upper airways
are not rigid... and therefore collapse
Ryan Chow: tongue? genioglossus

How do we generate a breath-inflate the

lung?
Have you got the Rhythm? Rhythmogenesis, where
does it originate? Ryan Chow: other motor units were recruited as breaths
continued
• Rhythmic pattern
– diaphragm motor units Ryan Chow: each spike represents a motor unit
– Orderly recruitment
• Esophageal Pressure
• Airflow à volume Ryan Chow: more negative --> inspiration

• Why more units as

inspiration progresses
• Does Mr. A.L. have the
rhythm?
• Is he missing a rhythm?
Ryan Chow: Yes... but he lacks the rhythm to the upper
airways
Ryan Chow: there's an imbalance

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Phrenic motoneuron discharge

Ryan Chow: innervates diaphragm
patterns

Ryan Chow: a single neuron

Single motorneurons
Ryan Chow: 1) rectify (absolute value)
Integrated nerve Ryan Chow: 2) integrate
recording
Ryan Chow: looks like tidal volume
Whole nerve recording
Ryan Chow: The Recruitment is due to the RECOIL OF
THE CHEST WALL
Milano et al., J.Appl.Physiol. 1992
Ryan Chow: ALL the neurons

How do we increase force/pressure generation?

1. Rate Coding (increased frequency of
discharge) Ryan Chow: b/c amplitude never changes

2. Recruitment of additional motorneurons

Why is it necessary for pressure generation to
increase (by recruitment and rate coding) during
inspiration?
Is this be true of a limb muscle?
No because the weight of the limb does not change...
unlike the chest wall which will experience recoil

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VOLUME
VT

FLOW
INSP.
• Resp.
0
EXP. Muscles
INTEGRATED
NERVE ACTIVITY
• “Pump”
PHRENIC N. DIAPHRAGM
vs
RECURRENT LARYNGEAL
LARYNGEAL N. ABDUCTION
Ryan Chow: the upper airway nerves would discharge
ROLLING • “Resistance” earlier?
HYPOGLOSSAL N. STONES
Ryan Chow: this is to prepare the upper airway to relax
airways
• note timing
TIME
Ryan Chow: mr. AL did not have this signal

Organization of brain stem respiratory

regions & rhythm
• Rythmogenesis: Located within the medulla
Lung afferents • Section between
in vagus n
medulla & spinal cord
Respiratory efferents – Halts respiration
in vagus n.
– higher Xn “minor”
effects

⌫⌫⌫ VRG = ventral respiratory group

DRG = dorsal respiratory group
NTS= nucleus tractus solitarius
NA = nucleus ambiguus
NRA = nucleus retroambiguus

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Breathing Pattern w transection of caudal
brainstem with/without vagotomy
Dorsal View Caudal
brainstem
PRG = pontine respiratory group
Rythmogenesis: Located within the medulla
Brainstem structures with respiratory neurons
Transverse Sections
Dorsal View Caudal
brainstem of medulla
PRG = pontine respiratory group
Nucleus RA I/E neurons cross midline to project to spinal cord
e.g. phrenic, intercostal & others
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I Rhythmic & normal
Vagi cut à impact of Ryan Chow: At I... breatihing remains!
release of vagal afferents
II PRG terminates inspiration Ryan Chow: At II w/ vagus cut... breathing has more
Vagi cut à apneusis or inhalation
inspiratory spasms, TI é
III medulla from pons Ryan Chow: Dorsal Respiratory Group: DRG Ventral
regular pattern of respiration Respirator Grouop: VRG
– independent of vagi
IV Between medullar and Ryan Chow: At III, more slow and deep breathing. W/
spinal cord respiration vagus cut... lung is held inflated
ceases
Ryan Chow: At IV... no breathing
VRG: long column resp
neurons containing:
larynx
- nucleus ambiguus, NA
- nucl. retroambiguus RA projects down spinal cord
- Botzinger complex &
- pre-Botzinger complex
- Mix of Inspiratory & Ryan Chow: Different regions project to different parts of
expiratory cells the body
- Segregated column of
neurons
- NA cell bodies project to
larynx via ipsilat vagus
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Brainstem structures with respiratory neurons

Transverse Sections
Dorsal View Caudal
brainstem of medulla

Pre-Botzinger Complex
…….
- Site of rhythmogenesis

- “Complex mechanisms”

- network of neurons
resulting in respiratory
Ryan Chow: but this doesn't tell us how rhythm is
rhythm
generated!
Google: Jack Feldman UCLA

Brainstem structures with respiratory neurons

Transverse Sections
Dorsal View Caudal DRG: dorsomedial medulla
brainstem of medulla
- subnucleus of solitary tract
- Afferents for
glossopharyngeal & vagus Ryan Chow: ie. upper airways
nerves
- i.e. carotid & aortic
bodies, Lung/airway
afferents from slowly
adapting and rapidly
adapting myelinated
receptors, as well as C-
fibres
- Predominantly Inspiratory
cells but some E cells

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Rhythmogenesis, facing the challenge of mammalian

neural microcircuits: taking a few breaths may help
PMN=premotor neurons
MN=motor neurons

Ryan Chow: currently... we use a pump to exert a positive

pressure in the upper airways (like a mask)

Ryan Chow: preBotzinger complex

Feldman & Kam: The Journal of Physiology593: 3-23, 2014 Ryan Chow: sleep apnea can lead to heart conditions
(arrhthmia in the heart)

Rhythmogenesis, facing the challenge of mammalian

neural microcircuits

Rhythmogenic microcircuits or Central

Pattern Generators (CPGs) provide neural
computations by circuits controlling Ryan Chow: other ex. swallowing
rhythmic movements that are limited to:
1. Rhythm generation –transformation of tonic drive
(rhythmic afferent input not needed) into repetitive
signals that determine the period of the cycle Ryan Chow: no afferent input is required!

2. Pattern generation –distribution and modulation of

this signal to activate participating muscles with
appropriate force and timing
Feldman & Kam: The Journal of Physiology593: 3-23, 2014

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Rhythmogenesis, facing the challenge of mammalian

neural microcircuits

Rhythmogenic microcircuits in mammals or

Central Pattern Generators (CPGs) should
meet 4 criteria:
1. Inhibition, silencing, or destruction of key elements of
the microcircuit significantly perturbs or stops rhythm!
- PreBotC 2008 in behaving rodents
2. Microcircuit projects to appropriate motoneuronal
populations (premotor to motor neurons 1991, 1994/5, 2008)
3. Modulatory afferents alter frequency (1996,2011,2013,
2014)
4. Isolated microcircuit (when sufficiently driven)
generates rhythmic activity ) in vitro slice 1991
Feldman & Kam: The Journal of Physiology593: 3-23, 2014

Spinal cord & control of breathing

Location of Phrenic,
intercostal & abdominal
motoneurons
Phrenic mn: longitudinal
oriented column
Intercostal mn: External/
Internal motor columns
through thoracic spinal cord
Abdominal mn: lower
thoracic & upper lumbar
cord

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Spinal cord & control of breathing

Descending tracts for spinal
respiratory motoneurons

Dorsal
Automatic respiratory drive
to breathe: ventrolateral
columns
Voluntary respiratory
control: corticospinal tract
in dorsolateral spinal cord

Ventral Can they be separated in

disease?

Medial Lateral

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