Inflammation-induced
release
of
prostaglandin
E2
(PGE2)
changes
breathing
patterns
and
the
response
to
CO2
levels.
This
may
have
fatal
consequences
in
newborn
babies
result
sudden
infant
death.
To
elucidate
underlying
mechanisms,
we
present
a
novel
brainstem
organotypic
culture
that
generates
rhythmic
neural
network
motor
activity
for
3
weeks.
We
show
increased
elicits
gap
junction-dependent
PGE2.
alters
preBötzinger
rhythm-generating
complex
chemosensitive
respiratory
regions,
thereby
increasing
sigh
frequency
depth
inspiration.
used
mice
lacking
eicosanoid
prostanoid
receptors
(EP3R),
slices
optogenetic
inhibition
EP3R+/+
cells
demonstrate
EP3R
is
important
ventilatory
hypercapnia.
Our
study
identifies
pathway
linking
inflammatory
systems,
with
implications
inspiration
sighs
throughout
life,
ability
autoresuscitate
when
fails.
Annual Review of Neuroscience,
Год журнала:
2022,
Номер
45(1), С. 223 - 247
Опубликована: Март 9, 2022
Breathing
is
a
vital
rhythmic
motor
behavior
with
surprisingly
broad
influence
on
the
brain
and
body.
The
apparent
simplicity
of
breathing
belies
complex
neural
control
system,
central
pattern
generator
(bCPG),
that
exhibits
diverse
operational
modes
to
regulate
gas
exchange
coordinate
an
array
behaviors.
In
this
review,
we
focus
selected
advances
in
our
understanding
bCPG.
At
core
bCPG
preBötzinger
(preBötC),
which
drives
inspiratory
rhythm
via
unexpectedly
sophisticated
emergent
mechanism.
Synchronization
dynamics
underlying
preBötC
rhythmogenesis
imbue
system
robustness
lability.
These
are
modulated
by
inputs
from
throughout
generate
rhythmic,
patterned
activity
widely
distributed.
connectivity
emerging
literature
support
link
between
breathing,
emotion,
cognition
becoming
experimentally
tractable.
bring
great
potential
for
elucidating
function
dysfunction
other
mammalian
circuits.
The Journal of Comparative Neurology,
Год журнала:
2018,
Номер
526(8), С. 1389 - 1402
Опубликована: Фев. 23, 2018
The
preBötzinger
Complex
(preBötC),
a
compact
medullary
region
essential
for
generating
normal
breathing
rhythm
and
pattern,
is
the
kernel
of
central
pattern
generator
(CPG).
Excitatory
preBötC
neurons
in
rats
project
to
major
breathing-related
brainstem
regions.
Here,
we
provide
connectivity
map
mice
both
excitatory
inhibitory
neurons.
Using
genetic
strategy
label
neurons,
confirmed
extensive
projections
within
CPG
including
contralateral
preBötC,
Bötzinger
(BötC),
ventral
respiratory
group,
nucleus
solitary
tract,
parahypoglossal
nucleus,
parafacial
(RTN/pFRG
or
alternatively,
pFL
/pFV
),
parabrachial
Kölliker-Füse
nuclei,
as
well
midbrain
periaqueductal
gray.
Interestingly,
paralleled
projections.
Moreover,
examined
overlapping
pons
detail
found
that
they
targeted
same
We
further
explored
direct
anatomical
link
between
suprapontine
brain
regions
may
govern
emotion
other
complex
behaviors
can
affect
be
affected
by
breathing.
Forebrain
efferent
were
sparse
restricted
specific
nuclei
thalamus
hypothalamus,
with
processes
rarely
observed
cortex,
basal
ganglia,
limbic
regions,
e.g.,
amygdala
hippocampus.
conclude
sends
direct,
presumably
inspiratory-modulated,
parallel
distinct
targets
throughout
generate
modulate
and/or
coordinate
behaviors,
physiology,
cognition,
emotional
state.
Annual Review of Neuroscience,
Год журнала:
2018,
Номер
41(1), С. 475 - 499
Опубликована: Май 1, 2018
Rhythmicity
is
a
universal
timing
mechanism
in
the
brain,
and
rhythmogenic
mechanisms
are
generally
dynamic.
This
illustrated
for
neuronal
control
of
breathing,
behavior
that
occurs
as
one-,
two-,
or
three-phase
rhythm.
Each
breath
assembled
stochastically,
increasing
evidence
suggests
each
phase
can
be
generated
independently
by
dedicated
excitatory
microcircuit.
Within
microcircuit,
rhythmicity
emerges
through
three
entangled
mechanisms:
(
a)
glutamatergic
transmission,
which
amplified
b)
intrinsic
bursting
opposed
c)
concurrent
inhibition.
triangle
dynamically
tuned
neuromodulators
other
network
interactions.
The
ability
coupled
oscillators
to
reconfigure
recombine
may
allow
breathing
remain
robust
yet
plastic
enough
conform
nonventilatory
behaviors
such
vocalization,
swallowing,
coughing.
Lessons
learned
from
respiratory
translate
highly
dynamic
integrated
rhythmic
systems,
if
approached
one
at
time.
The Journal of Physiology,
Год журнала:
2016,
Номер
594(6), С. 1529 - 1551
Опубликована: Янв. 10, 2016
Abstract
We
discuss
recent
evidence
which
suggests
that
the
principal
central
respiratory
chemoreceptors
are
located
within
retrotrapezoid
nucleus
(RTN)
and
RTN
neurons
directly
sensitive
to
[H
+
].
glutamatergic.
In
vitro
,
their
activation
by
]
requires
expression
of
a
proton‐activated
G
protein‐coupled
receptor
(GPR4)
proton‐modulated
potassium
channel
(TASK‐2)
whose
transcripts
undetectable
in
astrocytes
rest
lower
brainstem
network.
The
pH
response
is
modulated
surrounding
but
genetic
deletion
or
both
GPR4
TASK‐2
virtually
eliminates
chemoreflex.
Thus,
although
this
reflex
regulated
innumerable
brain
pathways,
it
seems
operate
predominantly
modulating
discharge
rate
neurons,
hypercapnia
may
ultimately
derive
from
intrinsic
sensitivity.
increase
lung
ventilation
stimulating
multiple
aspects
breathing
simultaneously.
They
stimulate
about
equally
during
quiet
wake
non‐rapid
eye
movement
(REM)
sleep,
lesser
degree
REM
sleep.
activity
inhibitory
feedback
excitatory
inputs,
notably
carotid
bodies.
latter
input
operates
normo‐
fails
activate
under
hypocapnic
conditions.
inhibition
probably
limits
hyperventilation
produced
hypoxia.
also
activated
inputs
serotonergic
hypothalamic
neurons.
absence
underlies
sleep
apnoea
lack
chemoreflex
characterize
congenital
hypoventilation
syndrome.
image
Reviews in the Neurosciences,
Год журнала:
2018,
Номер
30(2), С. 107 - 164
Опубликована: Дек. 13, 2018
Central
pattern
generators
(CPGs)
are
generally
defined
as
networks
of
neurons
capable
enabling
the
production
central
commands,
specifically
controlling
stereotyped,
rhythmic
motor
behaviors.
Several
CPGs
localized
in
brainstem
and
spinal
cord
areas
have
been
shown
to
underlie
expression
complex
behaviors
such
deglutition,
mastication,
respiration,
defecation,
micturition,
ejaculation,
locomotion.
Their
pivotal
roles
clearly
demonstrated
although
their
organization
cellular
properties
remain
incompletely
characterized.
In
recent
years,
insightful
findings
about
made
mainly
because
(1)
several
complementary
animal
models
were
developed;
(2)
these
enabled
a
wide
variety
techniques
be
used
and,
hence,
plethora
characteristics
discovered;
(3)
organizations,
functions,
cell
across
all
species
studied
thus
far
found
well-preserved
phylogenetically.
This
article
aims
at
providing
an
overview
for
non-experts
most
important
on
vivo
models,
vitro
preparations
from
invertebrate
vertebrate
well
primates.
Data
CPG
adaptation,
organization,
will
summarized
with
special
attention
paid
network
locomotion
given
its
advanced
level
characterization
compared
some
other
CPGs.
Similarities
differences
between
also
highlighted.