bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 11, 2024
Like
other
brain
circuits,
the
brainstem
respiratory
network
is
continually
modulated
by
neurotransmitters
that
activate
slow
metabotropic
receptors.
In
many
cases,
activation
of
these
receptors
only
subtly
modulates
motor
pattern.
However,
some
receptor
types
evokes
arrest
pattern
as
can
occur
following
µ-opioid
We
propose
varied
effects
neuromodulation
on
depend
neuromodulator
expression
and
their
influence
excitability
post-synaptic
targets.
Because
a
comprehensive
characterization
cellular
properties
across
remains
challenging,
we
test
our
hypothesis
combining
computational
modelling
with
ensemble
electrophysiologic
recording
in
pre-Bötzinger
complex
(pre-BötC)
using
high-density
multi-electrode
arrays
(MEA).
Our
model
encapsulates
neuromodulatory
transmission
organized
asymmetrically
to
promote
rhythm
generation.
To
this
hypothesis,
increased
strength
connections
used
selective
agonists
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 2, 2023
ABSTRACT
How
breathing
is
generated
by
the
preBötzinger
Complex
(preBötC)
remains
divided
between
two
ideological
frameworks,
and
persistent
sodium
current
(
I
NaP
)
lies
at
heart
of
this
debate.
Although
widely
expressed,
pacemaker
hypothesis
considers
it
essential
because
endows
a
small
subset
neurons
with
intrinsic
bursting
or
“pacemaker”
activity.
In
contrast,
burstlet
theory
dispensable
rhythm
emerges
from
“pre-inspiratory”
spiking
activity
driven
feed-forward
network
interactions.
Using
computational
modeling,
we
discover
that
changes
in
spike
shape
can
dissociate
bursting.
Consistent
many
experimental
benchmarks,
conditional
effects
on
during
simulated
oxygenation,
development,
extracellular
potassium,
temperature
alter
prevalence
pre-inspiratory
without
altering
role
.
Our
results
support
unifying
where
excitatory
interactions,
but
not
spiking,
are
critical
interdependent
features
preBötC
rhythmogenesis.
SIGNIFICANCE
STATEMENT
Breathing
vital
rhythmic
process
originating
complex.
Since
its
discovery
1991,
there
has
been
spirited
debate
about
whether
respiratory
generation
as
property
specialized
capabilities,
endowed
currents.
Here,
using
propose
data-driven
model
which
bridges
gap
these
competing
theories.
model,
both
cellular
properties
(a
current)
(recurrent
excitation),
bursting,
generation.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 11, 2024
Like
other
brain
circuits,
the
brainstem
respiratory
network
is
continually
modulated
by
neurotransmitters
that
activate
slow
metabotropic
receptors.
In
many
cases,
activation
of
these
receptors
only
subtly
modulates
motor
pattern.
However,
some
receptor
types
evokes
arrest
pattern
as
can
occur
following
µ-opioid
We
propose
varied
effects
neuromodulation
on
depend
neuromodulator
expression
and
their
influence
excitability
post-synaptic
targets.
Because
a
comprehensive
characterization
cellular
properties
across
remains
challenging,
we
test
our
hypothesis
combining
computational
modelling
with
ensemble
electrophysiologic
recording
in
pre-Bötzinger
complex
(pre-BötC)
using
high-density
multi-electrode
arrays
(MEA).
Our
model
encapsulates
neuromodulatory
transmission
organized
asymmetrically
to
promote
rhythm
generation.
To
this
hypothesis,
increased
strength
connections
used
selective
agonists
