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2020 - NEUR30002 - Lecture 28
2020 - NEUR30002 - Lecture 28
Neurophysiology
Respiratory system: Rhythm of life
Foundations of respiratory system
Dr Angelina Fong
angelina.fong@unimelb.edu.au
Department of Physiology
School of Biomedical Sciences
WARNING
Maintain Blood pH
Circulation
Oxygen
cascade Match metabolism
Pulmonary diffusion
Carefully coordinated
interaction between the
respiratory and
Circulation cardiovascular system
Oxygen (autonomic nervous
cascade system)
Tissue
diffusion
Tissue
metabolism
Department of Physiology, School of Biomedical Sciences
Breathing is continuous and automatic
Inspiration
Inspiration
VT
Inspiration
VT
http://123ery.deviantart.com/
Conscious control
(feed forward) Swallowing Vocalisation
Expiration
Laryngeal adductor Recurrent laryngeal
muscles nerve
Thoracic Intercostal
Internal intercostals
nerves
Abdominal muscles Abdominal nerves
Department of Physiology, School of Biomedical Sciences Del Negro, et al., 2018. Nature Rev. Neurosci. 19:351–367
Respiration is a 3 phase event In mammals
airflow
constriction
in
Subglottal
Pressure
pressure (mmHg) pressure (mmHg) dilation
Intra-alveolar
Recurrent
Laryngeal Branch of the vagus nerve
Intra-plural
Nerve
Phrenic
Volume of air
Nerve
moved (mL)
n
tio
ira
Diaphragm
sp
Insp
In
Department of Physiology, School of Biomedical Sciences
Respiration is a 3 phase event In mammals
airflow
constriction
in
Subglottal
Pressure
pressure (mmHg) pressure (mmHg) dilation
Intra-alveolar
Recurrent
Laryngeal
Intra-plural
Nerve
Phrenic
Volume of air
Nerve
moved (mL)
n
tio
n
ira
tio
Diaphragm
sp
in st-
ira
Insp Post
In
Po
-Insp
sp
Department of Physiology, School of Biomedical Sciences
Respiration is a 3 phase event In mammals
airflow
constriction
in
Subglottal
Pressure
pressure (mmHg) pressure (mmHg) dilation
Intra-alveolar
Recurrent
Laryngeal
Intra-plural
Nerve
Phrenic
Volume of air
Nerve
moved (mL)
n
tio
tio
n
ira
ra
tio
Diaphragm
pi
sp
in st-
ira
Insp Post Late
ex
In
Po
-Insp E
sp
te
La
Department of Physiology, School of Biomedical Sciences
What do you need to know
1. The pressure and airways changes in the three phases of respiratory rhythm
2. The nerves and muscles involved in the three phases of respiratory rhythm (as much
detail as was described in the lecture)
Dr Angelina Fong
angelina.fong@unimelb.edu.au
Department of Physiology
School of Biomedical Sciences
WARNING
Expiration
Laryngeal adductor Recurrent laryngeal
muscles nerve
Thoracic Intercostal
Internal intercostals
nerves
Abdominal muscles Abdominal nerves
Department of Physiology, School of Biomedical Sciences Del Negro, et al., 2018. Nature Rev. Neurosci. 19:351–367
Ventral respiratory group (VRG)
Source of respiratory rhythm?
Neonatal rodent brainstem-spinal cord preparation
VRG
VRG
Medulla
Hypoglossal C4
nerve
(CN XII)
Phrenic nerve
Cervical
spinal
cord PMN
External Intercostals
Phrenic Muscles (inspiratory)
nerve
Abdominal
PMN = Phrenic motor neurons Muscles
Smith et al., 1990. J. Neurophys. 64: 1149 - 1169
(expiratory)
Department of Physiology, School of Biomedical Sciences
Ventral respiratory group (VRG)
Source of respiratory rhythm?
Neonatal rodent brainstem-spinal cord preparation
VRG
VRG
Medulla
Hypoglossal C4
nerve
(CN XII)
Phrenic nerve
Cervical
spinal
cord PMN
External Intercostals
Phrenic Muscles (inspiratory)
nerve
Abdominal
PMN = Phrenic motor neurons Muscles
Smith et al., 1990. J. Neurophys. 64: 1149 - 1169
(expiratory)
Department of Physiology, School of Biomedical Sciences
pre-Bötzinger complex – the source of respiratory rhythm?
Modified from Alheid et al., Resp Physiol. Neurobiol., 2004
Smith et al., 1991,Science, 254: 726 - 729
CVLM
RVLM
BötC rVRG
cVRG
Pre-BötC
rostral caudal
Hypoglossal nerve
Dr Angelina Fong
angelina.fong@unimelb.edu.au
Department of Physiology
School of Biomedical Sciences
WARNING
Pre-BötC are:
Functionally • Pre-inspiratory neurones
(electrophysiological) or early Inspiratory
• Little to no expiratory neurones
Extracellular
recording
Phrenic nerve
recording
NAm
Pre-BötC
RVLM /
CVLM
Biotin =
recorded neurone NK1R
Department of Physiology, School of Biomedical Sciences Guyenet & Wang, 2001. J. Neurophysiol. 86:438-446.
Identity of pre-Bötzinger complex neurones Chemical marker
Pre-BötC are:
• No unique markers
NAm • Glutamatergic
Pre-BötC • Subset that is glycinergic
• NK1-receptor expressing
RVLM /
CVLM • Somatostatin (SST) expressing
• Dbx-1 (transcription factor) expressing
NK1-receptor expressing
Gray PA et al., 2001. Nature Neuroscience, 4: 927-930.
Fong & Potts, 2006. J. Physiol. 575: 869-885.
Biotin =
Stornetta et al., 2003. J. Comp. Neurol. 455:499-512
recorded neurone NK1R
Department of Physiology, School of Biomedical Sciences Guyenet & Wang, 2001. J. Neurophysiol. 86:438-446.
Neurokinin 1 receptors (NK1-R)
1.Endogenous ligand = substance P
2.G-protein coupled receptor
3.NK1-R internalised following stimulation by ligand
(substance P)
Attached ligand also internalised
ZAP = SAP
TA (Targeting agent) = Substance P
Department of Physiology, School of Biomedical Sciences
pre-Bötzinger complex – necessary for respiratory rhythm
Selective lesion of > 80% of NK1 receptor expressing cells in Pre-BötC using Saporin-Substance P
sigh
Control eupnea
apnea
SAP-SP
Ipeak 1.0
5ss
Gray PA et al., 2001. Nature Neuroscience, 4: 927-930.
Dr Angelina Fong
angelina.fong@unimelb.edu.au
Department of Physiology
School of Biomedical Sciences
WARNING
Question:
Can you explain why there addition
of SP (substance P) produces a small
return of bursts?
FFA = flufenamic acid blocks Ca2+ activated nonselective cationic current (ICaN)
Del Negro et al., 2005. J. Neurosci. 25: 446-453.
SOM = somatostatin
Rat
NAm
Pre-BötC
RVLM /
CVLM
IO
Department of Physiology, School of Biomedical Sciences Schwarzacher et al., 2011. Brain. 134: 24-35.
Human pre-Bötzinger Complex
MSA =
multiple system atrophy
SCA3 =
spinocerebellar ataxia type 3 brains
Click here to access Poll Everywhere. (Does not require live presentation)
Department of Physiology, School of Biomedical Sciences
Click here to access Poll Everywhere. (Does not require live presentation)
Department of Physiology, School of Biomedical Sciences
What you need to know
1. Pre-BötC neurones have intrinsic bursting properties
2. Production of respiratory rhythm is an emergent property of the pre-Bötzinger
complex
3. Evidence from humans support the importance of the pre-Bötzinger complex in
respiratory function