Transcript Roger Dampney lecture Boston-revised for web

The Brain and the Cardiovascular System
Roger Dampney, Ph.D.
Physiology, School of Medical Sciences and Bosch Institute
The University of Sydney, Australia
“The coordinated physiological reactions which maintain most of
the steady states in the body are so complex, and so peculiar to the
living organism, that it has been suggested that a specific
designation for these states be employed – homeostasis”
Walter Bradford Cannon,
MA, MD (1871–1945),
circa 1908. History of
Medicine Division, National
Library of Medicine.
“… the integrated cooperation of a wide range of organs- brain
and nerves, heart, lungs, kidneys, spleen - which are promptly
brought into action when conditions arise which might alter the
blood in its respiratory services.”
How is this cooperation achieved?
(1) Feedback (reflex) regulation
(2) Feedforward regulation (central command)
Fig. 1. From Krogh A, Lindhard J. J Physiol
47: 112-136, 1913.
Freely available at
onlinelibrary.wiley.com/doi/10.1113/jphysiol.
1913.sp001616/pdf
“At the beginning of heavy work … there
is an abrupt rise in pulmonary ventilation
and heart rate. The blood flow (as
indicated by the oxygen absorption in
the lungs) is increased rapidly but very
evenly.”
“Evidence is brought forward to show
that the rise in ventilation like the
increase in heart rate is not produced
reflexly but by irradiation of impulses
from the motor cortex.”
Feed-forward control (central command)
EXAMPLE: exercise
motor cortex
hypothalamic and
brainstem centers
increase in sympathetic
activity
increase in
blood
pressure
Conscious, paralysed, artificially
ventilated human subject
Fig. 6A. From Gandevia et al. J. Physiol. 470: 85107, 1993.
Freely available at
onlinelibrary.wiley.com/doi/10.1113/jphysiol.1993.
sp019849/pdf
“Central command” can evoke integrated
cardiorespiratory responses
EXAMPLE: exercise
motor cortex
hypothalamic and
brainstem centers
Sympathetic
activity
Cardiac
output
Blood
pressure
Respiratory
activity
Ventilation
Oxygen delivery
Baroreceptor reflex
% contribution of cardiac
output (CO) and total
peripheral resistance (TPR)
to baroreflex changes in
arterial pressure
Arterial pressure
TPR
Baroreceptor firing rate
CO
100
Brainstem centres
Sympathetic
vasomotor
activity
Vascular
resistance
Sympathetic
cardiac
activity
Cardiac
contractility
Arterial pressure
Vagal cardiac
activity
50
Heart rate
0
Cardiac
output
At
rest
During
exercise
Modified from Raven et al. Exp Physiol 91: 37-49, 2006.
Freely available at
onlinelibrary.wiley.com/doi/10.1113/expphysiol.2005.032250/full
Baroreceptor reflex is re-set during exercise
Fig. 2. From Miki et al. J Physiol 548: 313-322,
2003.
Freely available at
onlinelibrary.wiley.com/doi/10.1111/j.14697793.2003.00313.x/full
The baroreflex function curves are determined
by increasing or decreasing the arterial
pressure (Pa) with vasoconstrictor or
vasodilator drugs (e.g., phenylephrine and
nitroprusside, as shown in the next slide). This
produces a reflex decrease or increase,
respectively, in heart rate and sympathetic
activity. The relationship between input (Pa)
and output (e.g., renal sympathetic nerve
activity, RSNA) is then plotted on a graph.
•Threshold (T) increased
•Saturation point (S) increased
•Gain of the baroreflex is increased
•Therefore the baroreflex has a higher
operating range of pressure with
undiminished sensitivity
The above baroreflex function curves were determined in a conscious rat before and during
exercise. They show clearly that the reflex is still very effective during exercise but is reset
to operate at higher levels of both arterial pressure and sympathetic activity.
HR (bpm)
MAP (mmHg)
Cardiovascular responses to psychological stress
Baroreflex resetting
130
120
110
control
100
480
stress
440
400
360
RSNA (nu)
240
180
120
Air jet stress
60
0
5
10
Time (min)
RSNA: renal sympathetic nerve activity
15
Baroreflex operates at higher levels of MAP
and RSNA with increased sensitivity
Figs. 2 & 4. From Kanbar et al. Am J Physiol 292:R362-R367, 2007.
Reprinted with permission.
Freely available at ajpregu.physiology.org/content/292/1/R362
Circadian rhythms in cardiovascular variables
NB: There are parallel changes in arterial
pressure and heart rate, associated with
the sleep-wake cycle.
Fig. 4.2. From Low PA,
Benarroch EE (eds.)
Clinical Autonomic
Disorders. Philadelphia,
PA: Lippincott Williams &
Wilkins, 2008.
What is the role of the baroreflex in
regulating arterial pressure under these
conditions?
The baroreflex is always operational,
but is continuously being reset
according to the behavioural conditions
(e.g., sleep-wake cycle, arousal,
exercise, etc.).
Set-point and gain of the
control system can be altered
by other centers in the brain
heart & blood vessels
e.g., arterial
pressure
brainstem centers & autonomic
outflow to heart & blood vessels
carotid sinus and
aortic baroreceptor
afferent nerves
baroreceptors
Chemoreceptor reflex
Hypoxia
Fig. 1, right. From
Smith KA, Yuan JX-J.
Am J Physiol 303:
C911-C912, 2012.
Reprinted with
permission.
Freely available at
ajpcell.physiology.org/
content/303/9/C911.
Chemoreceptor afferent
activity
Respiratory
activity
Ventilation
(liters/min)
40
30
Reflex effects
increase greatly
when PO2 falls below
~ 60 mmHg
20
Ventilation
Sympathetic
vasomotor
activity
Vasoconstriction
Cardiac
vagal
activity
Heart rate &
cardiac work
10
0
40
60
80
100
Arterial blood PO2 (mmHg)
Modified from Fig. 18.33 in Human Physiology,
(5th ed), O.H. Peterson (ed). Blackwell, 2007.
Oxygen uptake
Oxygen conservation
Chemoreflex is enhanced during exercise
150
∆ vascular
conductance
60
Intense
exercise
50
100
Ventilation
(liters/min)
40
Moderate
exercise
20
10
Rest
50
0
30
Moderate
exercise
Alpha
receptor
block
Chemoreceptor
block
Alpha
receptor
block
Chemoreceptor
block
Modified from Dempsey JA. J Physiol 590: 4129-4140, 2012.
Freely available at
onlinelibrary.wiley.com/doi/10.1113/jphysiol.2012.233908/pdf
Rest
0
30
50
70
90
110
130
pAO2 (mmHg)
Modified from Weil et al. J Appl Physiol 33: 813-819,
1972.
Freely available at jap.physiology.org/content/33/6/813
Reflex ventilatory response is amplified
Chemoreceptor reflex blockade has very
little effect at rest but increases vascular
conductance during exercise
Chemoreceptor reflex contributes about 30%
of sympathetically mediated vasoconstriction
during exercise
Chemoreflex is enhanced
in heart failure
Sympathetic activity is normalized
in heart failure by carotid body denervation
Fig. 1B. From Marcus et al. J Physiol 592: 391-408, 2014.
Freely available at
onlinelibrary.wiley.com/doi/10.1113/jphysiol.2013.266221/pdf
Fig. 3. From Sun et al. J Appl Physiol 86: 1264-1272, 1999.
Reprinted with permission.
Freely available at jap.physiology.org/content/86/4/1264
The diving (nasopharyngeal) reflex is the most
powerful cardiorespiratory reflex known
smoke (rabbit)
Inspn
Respn
Expn
200
Fig. 5. From Greaves et al. Physiol
Biochem Zool 78: 9-17, 2005.
Available at
jstor.org/stable/10.1086/425201
Arterial
Pressure
(mmHg)
Mesenteric
blood flow
(mL/min)
100
0
80
40
0
480
Heart
rate
240
(beats/min)
0
Fig. 1. From White et al. Am J Physiol 228:404-409, 1975.
Reprinted with permission. Available at ajplegacy.physiology.org/content/228/2/404
Diving (human)
Sympathetic
Nerve recording
Fig. 1. From Fagius J, Sundlof G. J Physiol 377:
429-443, 1986
Freely available at
onlinelibrary.wiley.com/doi/10.1113/jphysiol.1986.
sp016196/pdf
Submersion (or irritant stimulus)
Nasopharyngeal
reflex
Nasopharyngeal receptor
activity
NB: MAP relatively
unchanged (=CO x TPR)
Via facial or trigeminal
afferents & brainstem centers
Sympathetic
vasomotor activity
Apnea
Intense peripheral
vasoconstriction
(except in brain & heart)
Total peripheral
resistance (TPR)
Cardiac vagal
activity
Heart rate (and
cardiac work)
Oxygen conservation
Cardiac
output (CO)
Interactions between reflexes: example
Submersion
(e.g., diving)
Hypoxia
Nasopharyngeal
receptor activity
Arterial chemoreceptor
activity
excitation
inhibition
Respiratory
activity
X
X
Heart
rate
X
Vascular
resistance
Pulmonary stretch
receptor activity
X
Chemoreceptor stimulation normally increases respiratory activity, but in presence of
inputs from nasopharyngeal receptors apnoea occurs. But chemoreceptor &
nasopharyngeal inputs summate to further increase reflex effects on vascular resistance
and heart rate. When respiratory activity increases, inputs from pulmonary stretch
receptors tend to reflexly increase heart rate and decrease vascular resistance.
Exercise
induced by
stimulation
of ventral roots
Fig. 1. McCloskey DI, Mitchell
JH. J Physiol 224: 173-186,
1972.
Freely available at
onlinelibrary.wiley.com/doi/10.11
13/jphysiol.1972.sp009887/pdf
Fig. 2, top and bottom.
McCloskey DI, Mitchell JH. J
Physiol 224: 173-186, 1972.
Freely available at
onlinelibrary.wiley.com/doi/10.11
13/jphysiol.1972.sp009887/pdf
The receptors subserving this effect are mechanoreceptors and chemoreceptors in
the skeletal muscle, innervated by myelinated group III and unmyelinated group IV
afferent fibers, respectively
Nucleus tractus solitarius (NTS)
Nucleus ambiguus (NA)
Ventral respiratory group (VRG)
Rostral ventrolateral medulla (RVLM)
Medulla oblongata (rat)
rostral level
Vagal preganglionic
neurons, regulating
heart rate
RVLM neurons
(regulating sympathetic
outflow to heart, blood
vessels, adrenal medulla)
caudal level
IX and X afferent fibres
from visceral receptors in
CV system, lungs, gut,
etc. (e.g., from
baroreceptors,
chemoreceptors and lung
inflation receptors)
VRG neurons
(controlling
respiratory
activity)
INPUTS
Arterial baroreceptors
Arterial chemoreceptors
Central projections of afferent inputs
reflexly affecting sympathetic activity
Nucleus of solitary
tract (NTS)
Cardiopulmonary receptors
Skeletal muscle receptors
Dorsal horn of
spinal cord
Rostral
ventrolateral
medulla (RVLM)
Spinal cord
Vestibular receptors
Nasopharyngeal receptors
Medullary
vestibular (VIII)
nucleus
Medullary
trigeminal (V)
nucleus
Sympathetic outflow
Direct projection
Direct and indirect
projections
Application of glycine to localized region on the ventral surface of the
medulla (“glycine-sensitive area”) causes profound hypotension
Glycine-sensitive
area
Glycine-sensitive
area
Modified from Guertzenstein PG, Silver A. J. Physiol. (Lond.)
242: 489-503, 1974. Freely available at
onlinelibrary.wiley.com/doi/10.1113/jphysiol.1974.sp010719/pdf
…due to inhibition of RVLM neurons
Baroreceptor reflex pathways
Inputs from
higher centers
Chemoreceptor reflex pathways
Nucleus tractus solitarius (NTS)
Nucleus ambiguus (NA)
Ventral respiratory group (VRG)
Rostral ventrolateral medulla (RVLM)
Medulla oblongata (rat)
rostral level
Vagal preganglionic
neurons, regulating
heart rate
RVLM neurons
(regulating sympathetic
outflow to heart, blood
vessels, adrenal medulla)
caudal level
IX and X afferent fibers
from visceral receptors in
CV system, lungs, gut,
etc. (e.g., from
baroreceptors,
chemoreceptors and lung
inflation receptors)
VRG neurons
(controlling
respiratory
activity)
How are the homologous cardiovascular & respiratory nuclei
identified in the human medulla?
In the case of the RVLM, most of the sympathetic
premotor neurons as identified in rats and rabbits
synthesize catecholamines and contain receptors
for angiotensin II.
Catecholamine neurons
Angiotensin II receptor binding
Human medulla (rostral level). Adapted from Fig. 3 in
Macefield VG & Henderson LA. Human Brain Mapping 31: 539549, 2010. Available at
onlinelibrary.wiley.com/doi/10.1002/hbm.20885/abstract
Fig. 5c. From Halliday et al. J Comp Neurol 273:
301-317, 1988. Available at
onlinelibrary.wiley.com/doi/10.1002/cne.902730
303/pdf
Adapted from Allen et al. J Comp Neurol 269:
249-264, 1988. Available at
onlinelibrary.wiley.com/doi/10.1002/cne.9026902
09/pdf
The region in the human lateral medulla that contains
a high density of Ang II receptors and catecholamine
neurons is homologous to the RVLM in other animals
Adapted from Fig. 326 in Ranson SW, Clark SL. The Anatomy of the
Nervous System. Philadelphia, PA: WB Saunders, 1959.
RVLM in humans is activated when sympathetic activity is reflexly
increased: an fMRI study
Subjects were asked to make a maximal
inspiratory breath-hold, which causes a reflex
increase in sympathetic activity to muscle blood
vessels (MSNA) (right panel), while their brain
activity was measured using functional magnetic
resonance imaging (fMRI). This resulted in
increased activity (BOLD signal) (panel below
left) in a region corresponding to the RVLM
(panel below right).
Right: Fig. 1. From Macefield et al. J Appl Physiol 100:266273, 2006. Reprinted with permission. Freely available at
jap.physiology.org/content/100/1/266
Stimulus
Medullary section
Allen et al., 1991
RVLM
Modified from Fig. 8 (left panel) and Fig. 3 (right panel) in Macefield VG & Henderson LA. Human Brain Mapping 31:539-549,
2010. Available at onlinelibrary.wiley.com/doi/10.1002/hbm.20885/abstract
RVLM sympathetic premotor neurons
CVLM: caudal ventrolateral medulla
IML: intermediolateral cell column
KF: Kölliker-Fuse nucleus (pons)
NTS: nucleus tractus solitarius
PAG: periaqueductal grey (midbrain)
PVN: paraventricular nucleus
(hypothalamus)
RVLM: rostral ventrolateral medulla
Modified from Fig. 4. Dampney RA.
Physiol Rev 74: 323-364, 1994.
Freely available at
physrev.physiology.org/content/74/2/323
RVLM neurons:
• project directly to sympathetic preganglionic neurons in spinal cord
• are tonically active, and this tonic activity maintains resting sympathetic activity and
hence resting blood pressure
• receive inputs (excitatory and inhibitory) from a wide range of peripheral receptors and
from cardiovascular nuclei in the pons, midbrain, and forebrain
• are a critical component of baroreceptor and other cardiovascular reflex pathways, as
well as pathways mediating cardiovascular responses from higher centers
Premotor sympathetic neurons in RVLM consist of
subgroups that regulate specific vascular beds
250
Point A
Point B
BPBP
(mmHg)
(mmHg)
Sympathetic outflow to
different vascular beds:
100
2
4
Skin symp
Skin SNA
activity
(imp/sec)
(imp/sec)
BP
(mmHg)
0
0
5
10
0
0
Muscle symp
Muscle SNA
activity
(imp/sec)
(imp/sec)
Modified from Fig. 2, B&C. From
Dampney RAL, McAllen RM. J Physiol
395:41-56, 1988. Freely available at
onlinelibrary.wiley.com/doi/10.1113/jphy
siol.1988.sp016907/pdf
Glu
1 min
Glu
Modified from McAllen et al. Clin Exp Hypertens
19: 607-618., 1997 Available at
informahealthcare.com/doi/pdf/10.3109/106419697
09083173
Descending pathways to spinal
sympathetic preganglionic neurons
HYPOTHALAMUS
PONS
MEDULLA
SPINAL CORD
Heart and
blood vessels
Adapted from Strack et al. Brain Res 491: 156-162, 1989.
Available at sciencedirect.com/science/article/pii/000689938990098X
Thermoregulatory reflex for cold
defense
Cold ambient temperature
AUTONOMIC
Sympathetic
activity to skin
blood vessels
SOMATOMOTOR
Skin cold receptor activity
Sympathetic activity to
piloerector muscle
Sympathetic activity
to brown adipose
tissue (BAT)
Fusimotor activity
to skeletal muscle
Shivering
Vasoconstriction
Skin
insulation
Metabolic
activity
Heat conservation
Heat production
Central thermoregulatory pathways
Fig. 6. From McKinley et al. Acta Physiologica 1 APR 2015.
Freely available at
onlinelibrary.wiley.com/doi/10.1111/apha.12487/full
dLPB dorsal lateral parabrachial nucleus
DMH Dorsomedial hypothalamus
eLPB external lateral parabrachial nucleus
MnPO Median preoptic nucleus
PO Preoptic area
RP Raphe pallidus
Skin vasoconstriction inhibited
BAT, shivering thermogenesis inhibited
Functional specificity of sympathetic outflow
to cardiovascular system
Receptor
activated
Muscle
vasoconstrictor
Baroreceptors
Chemoreceptors
Skin cold
receptors
~
Skin
vasoconstrictor
Cardiac
sympathetic
Hypothalamic mechanisms maintaining water balance
Cardiac
output
Dehydration
Arterial
pressure
OVLT
Blood osmolarity
SON
Renin release
OVLT
Angiotensin II
level
SFO & OVLT
SON
Vasopressin
release
Sympathetic nerve
activity
Organum vasculosum lamina
terminalis
Paraventricular nucleus
Subfornical organ
Supraoptic nucleus
C-Fos expression
Control
Hyperosmotic
SON
Drinking
Arterial
pressure
Reabsorption of
water in kidneys
PVN
SFO
SON
Higher
integrative
centers
PVN
SFO
PVN
PVN
Restoration of
fluid balance
Fig. 5, left & right columns. From Ho et al. (2007) Am J Physiol
292: R1690-R1698, 2007. Reprinted with permission.
Freely available at ajpregu.physiology.org/content/292/4/R1690
Central pathways regulating water balance
DMH Dorsomedial hypothalamus
MnPO Median preoptic nucleus
OVLT Organum vasculosum
lamina terminalis
PVN Paraventricular nucleus
PVT Paraventricular nucleus
of thalamus
SFO Subfornical organ
SON Supraoptic nucleus
Fig. 4. From McKinley et al. Acta Physiologica
1 APR 2015.
Freely available at
onlinelibrary.wiley.com/doi/10.1111/apha.1248
7/full
The subfornical organ (SFO) is a critical site at which hormones
can affect cardiovascular function
•
•
•
•
Apart from angiotensin II and sodium ions, other circulating substances (e.g., leptin,
cytokines, atrial natriuretic factor) can activate SFO neurons
Experimental hypertension induced by chronic infusion of angiotensin II is associated with
increased production of reactive oxygen species (ROS); blockade of ROS production in
SFO prevents angiotension II-induced hypertension (Zimmerman et al. Circ Res 95: 210216, 2004; circres.ahajournals.org/content/95/2/210/F2.expansion.html)
Infusion of leptin (hormone derived from adipose tissue) induces an increase in renal
sympathetic nerve activity; blockade of leptin receptors in the SFO prevents this effect
(Young et al. Hypertension 61: 737-744, 2013; hyper.ahajournals.org/content/61/3/737.full)
Circulating pro-inflammatory cytokines act on the brain to increase blood pressure, heart
rate and sympathetic activity; these effects are blocked by lesions of the SFO (Wei et al.
Hypertension 62: 118-125, 2013; hyper.ahajournals.org/content/62/1/118.full)
ROS in SFO - control
Circulating factors
SFO
Fig. 2A, left top
PVN
Fig. 2A, left bottom
ROS in SFO after
Ang II infusion
RVLM
Spinal cord
Fig. 2A, right top Day 16
From Zimmerman et al. Circ Res 95: 210-216, 2004.
Freely available at
circres.ahajournals.org/content/95/2/210/F2.expansion.html
Sympathetic activity
Cardiovascular and respiratory changes associated with behavior
- example of defensive behavior
CORTICAL
cortex
Conditioned
stimulus
SUB-CORTICAL
amygdala
hippocampus
thalamus
midbrain
Acute
psychological
stressor BRAINSTEM
Modified from LeDoux J. Current Biology
17(20): R868-R874, 2007.
Freely available at sciencedirect.com/science/
article/pii/S0960982207017794
Sympathetic
activity
hypothalamus
pons/
medulla
Respiratory
activity
Hormone
release
Motor activity
(e.g., freezing)
Key brain regions generating responses to psychological stress
mPFC
PAG
PVN
DMH
PeF
NTS
Amy
RVLM
Adapted from Fig. 7C in Müller-Ribeiro et al. Am J Physiol 307: R1025-R1035, 2014.
Freely available at ajpregu.physiology.org/content/307/8/R1025
Adapted from
Fig. 1 from
Stotz-Potter et
al J Neurosci
16: 1172-1179,
1996.
Freely
available at
jneurosci.org/c
ontent/16/3/11
73.full.pdf+html
Amy: amygdala
DA: dorsal hypothalamic area
DMH: dorsomedial hypothalamus
f: fornix
mPFC: medial prefrontal cortex
mt: mamillothalamic tract
NTS: nucleus tractus solitarius
PAG: periaqueductal gray
PeF: perifornical area
PH: posterior hypothalamus
PVN: paraventricular nucleus
RVLM: rostral ventrolateral medulla
VMH: ventromedial hypothalamus
Fig. 59. From Paxinos G &
Watson C. The Rat Brain in
Stereotaxic Coordinates.
Elsevier 2004.
DMH mediates the CV response to psychological stress
150
∆ Heart
rate
(bpm)
100
50
0
∆ Mean
arterial
pressure
(mmHg)
30
20
10
Control
0
Muscimol in DMH
0
4
8
12
16
20
Time (min)
Onset of air-jet stress
Muscimol in PVN
Modified from Figs. 1& 2. Stotz-Potter et al. J Neurosci 16: 1173-1179, 1996. Freely available at jneurosci.org/content/16/3/1173.full.pdf
via cortex & amygdala
Acute psychological
stressor
DMH
Baroreflex
resetting
Baroreceptor
inputs
NTS
CVLM
RVLM
Premotor
nucleus
(RVMM?)
Medullary
raphe
Central
respiratory
nuclei
Sympathetic
outflow
Sympathetic
outflow
Phrenic
nucleus
What about the midbrain PAG?
known connection
unknown connection
BAT: brown adipose tissue
Visceral
vasoconstriction
Heart rate
Cutaneous
vasoconstriction
BAT activity
Respiratory
activity
PAG columns: generate different
behavioral/autonomic patterns
Flight or freezing
Increased BP and HR
Visceral vasoconstriction
Hindlimb vasodilation
PAG
Adapted from Fig. 7C in Müller-Ribeiro et al. Am
J Physiol 307: R1025-R1035, 2014.
Freely available at
ajpregu.physiology.org/content/307/8/R1025
Active coping strategies Active coping strategies
Dorsolateral (dl)
Lateral (l)
Ventrolateral (vl)
Active coping strategies evoked
from lPAG and dlPAG
Passive coping strategies
evoked from vlPAG
Quiescence
Decreased BP and HR
Decreased sympathetic
activity
Modified from Fig. 1. Bandler et al. Brain Res Bull 53:95-104,
2000. Available at
sciencedirect.com/science/article/pii/S0361923000003130
The DMH mediates responses from dlPAG
Adapted from
Fig. 7C in
Müller-Ribeiro et
al. Am J Physiol
307: R1025R1035, 2014.
Freely available
at
ajpregu.physiolo
gy.org/content/3
07/8/R1025
PAG
NTS
DMH
RP
NTS: nucleus tractus solitarius
PNA: phrenic nerve activity
RP: raphe pallidus
RVMM: rostral ventromedial medulla
VRG: ventral respiratory group
VRG
RVMM
PNA
Heart Rate
SNA
Respiratory
Rate
Baroreflex
resetting
Psychological stressor
(e.g., sight/sound/odor of
predator, or perceived threat)
Proposed scheme
DMH
via cortex and
hypothalamus
dlPAG
lPAG
via spinal cord
and brainstem
Somatosensory stressor
(e.g., painful stimulus)
Modified from Fig. 11 in Horicuhi et al. J
Physiol 587: 5149-5162, 2009.
Freely available at
onlinelibrary.wiley.com/doi/10.1113/jphysiol.2
009.179739/full
Pons/medulla
Cardiovascular
response
Behavioral
response
Respiratory
response
Orexin (hypocretin) neurons are confined to the PeF/DMH
and have widespread projections
Fig. 14. From Peyron et al. J.
Neurosci. 18: 9996-10015, 1998.
Freely available at
jneurosci.org/content/18/23/9996.full
Orexin neurons are believed to play a role in various functions, including feeding
behavior, energy expenditure, the sleep-wake cycle, and defensive behavior
Orexin neurons regulate cardiovascular responses to
arousal or psychological stress
Resting
Exploration
* Orexin neurons are activated during arousal
or psychological stress (e.g., exposure to
novel environment)
Fig. 1, top and middle rows. From Furlong et al. Eur
J Neurosci 30: 1603-1614, 2009.
Available at
onlinelibrary.wiley.com/doi/10.1111/j.1460- * Blockade of orexin receptors reduce
9568.2009.06952.x/full
cardiovascular responses to psychological
stress
Orexin neurons
450
Heart rate
(bpm)
Activated orexin
neurons
Control
After orexin receptor blockade
400
350
Modified from Fig. 6. From
Furlong et al. Eur J
Neurosci 30: 1603-1614,
2009.
Available at
onlinelibrary.wiley.com/doi/
10.1111/j.14609568.2009.06952.x/full
300
Novel environment
CONCLUSION: Orexin neurons are activated during different behaviors and act to amplify
the cardiovascular and respiratory responses associated with those behaviors, i.e., they act
as a gain controller
Acknowledgements
The support of the following granting agencies is gratefully acknowledged:
The National Health and Medical Research Council of Australia
The National Heart Foundation of Australia
The Australian Research Council
Roger Dampney, Ph.D.
Emeritus Professor
Physiology, School of Medical Sciences Bosch Institute
[email protected]
Dr. Roger Dampney is Emeritus Professor in Cardiovascular
Neuroscience at the University of Sydney, Australia. He received
his PhD degree from the University of Sydney in 1973, and
conducted post-doctoral research with Don Reis at Cornell
Medical College in New York and with Alberto Zanchetti at the
University of Milan, Italy. Dr. Dampney is a leading investigator
in the study of the functional organization of central
cardiovascular pathways, with a particular interest in the
mechanisms by which the brain produces highly coordinated
cardiorespiratory changes that are appropriate for different
behaviors, such as exercise and defensive behavior. His
publications have received over 7500 citations. He has served
on the editorial board of several journals and has supervised
scores of students and fellows.
To receive a complete set of unaltered slides, please contact the APS Education Office ([email protected])