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
The Journal of Physiology,
Год журнала:
2024,
Номер
602(5), С. 809 - 834
Опубликована: Фев. 14, 2024
Abstract
Breathing
behaviour
involves
the
generation
of
normal
breaths
(eupnoea)
on
a
timescale
seconds
and
sigh
order
minutes.
Both
rhythms
emerge
in
tandem
from
single
brainstem
site,
but
whether
how
cell
population
can
generate
two
disparate
remains
unclear.
We
posit
that
recurrent
synaptic
excitation
concert
with
depression
cellular
refractoriness
gives
rise
to
eupnoea
rhythm,
whereas
an
intracellular
calcium
oscillation
is
slower
by
orders
magnitude
rhythm.
A
mathematical
model
capturing
these
dynamics
simultaneously
generates
frequencies,
which
be
separately
regulated
physiological
parameters.
experimentally
validated
key
predictions
regarding
signalling.
All
vertebrate
brains
feature
network
oscillator
drives
breathing
pump
for
regular
respiration.
However,
air‐breathing
mammals
compliant
lungs
susceptible
collapse,
rhythmogenic
may
have
refashioned
ubiquitous
signalling
systems
produce
second
rhythm
(for
sighs)
prevents
atelectasis
without
impeding
eupnoea.
image
Key
points
simplified
activity‐based
preBötC
inspiratory
neuron
population.
Inspiration
attributable
canonical
excitatory
mechanism.
Sigh
emerges
The
predicts
perturbations
uptake
release
across
endoplasmic
reticulum
counterintuitively
accelerate
decelerate
rhythmicity,
respectively,
was
validated.
Vertebrate
evolution
adapted
existing
mechanisms
slow
oscillations
needed
optimize
pulmonary
function
mammals.
Inspiratory
breathing
rhythms
arise
from
synchronized
neuronal
activity
in
a
bilaterally
distributed
brainstem
structure
known
as
the
preBötzinger
complex
(preBötC).
In
vitro
slice
preparations
containing
preBötC,
extracellular
potassium
must
be
elevated
above
physiological
levels
(to
7–9
mM)
to
observe
regular
rhythmic
respiratory
motor
output
hypoglossal
nerve
which
preBötC
projects.
Reexamination
of
how
K
+
affects
has
revealed
that
low-amplitude
oscillations
persist
at
levels.
These
oscillatory
events
are
subthreshold
standpoint
transmission
and
dubbed
burstlets.
Burstlets
neural
rhythmogenic
subpopulation
within
some
instances
may
fail
recruit
larger
network
events,
or
bursts,
required
generate
output.
The
fraction
(burstlet
fraction)
decreases
sigmoidally
with
increasing
potassium.
observations
underlie
burstlet
theory
rhythm
generation.
Experimental
computational
studies
have
suggested
recruitment
non-rhythmogenic
component
population
requires
intracellular
Ca
2+
dynamics
activation
calcium-activated
nonselective
cationic
current.
this
study,
we
show
calcium
driven
by
synaptically
triggered
influx
well
release/uptake
endoplasmic
reticulum
conjunction
current
can
reproduce
offer
an
explanation
for
many
key
properties
associated
Altogether,
our
modeling
work
provides
mechanistic
basis
unify
wide
range
experimental
findings
on
generation
preBötC.
Scientific Reports,
Год журнала:
2022,
Номер
12(1)
Опубликована: Фев. 21, 2022
Breathing
depends
on
interneurons
in
the
preBötzinger
complex
(preBötC)
derived
from
Dbx1-expressing
precursors.
Here
we
investigate
whether
rhythm-
and
pattern-generating
functions
reside
discrete
classes
of
Dbx1
preBötC
neurons.
In
a
slice
model
breathing
with
~
5
s
cycle
period,
putatively
rhythmogenic
Type-1
neurons
activate
100-300
ms
prior
to
Type-2
neurons,
specialized
for
output
pattern,
300-500
inspiratory
motor
output.
We
sequenced
transcriptomes
identified
differential
expression
123
genes
including
ionotropic
receptors
(Gria3,
Gabra1)
that
may
explain
their
preinspiratory
activation
profiles
Ca
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Авг. 8, 2023
Abstract
Inhibitory
neurons
embedded
within
mammalian
neural
circuits
shape
breathing,
walking,
chewing,
and
other
rhythmic
motor
behaviors.
At
the
core
of
circuit
controlling
breathing
is
preBötzinger
Complex
(preBötC),
a
nucleus
in
ventrolateral
medulla
necessary
for
generation
inspiratory
rhythm.
In
preBötC,
recurrently
connected
network
glutamatergic
Dbx1-derived
(Dbx1
+
)
generates
drive.
Functionally
anatomically
intercalated
among
preBötC
Dbx1
are
GABAergic
(GAD1/2
glycinergic
(GlyT2
neurons,
whose
roles
remain
unclear.
To
elucidate
inhibitory
microcircuits
we
first
characterized
spatial
distribution
molecularly-defined
subpopulations
double
reporter
mice
expressing
either
red
fluorescent
protein
tdTomato
or
EGFP
GlyT2
,
GAD1
GAD2
neurons.
We
found
that,
neonatal
mice,
majority
expressed
combination
while
much
smaller
subpopulation
also
GAD1.
determine
functional
role
these
subpopulations,
used
holographic
photostimulation,
patterned
illumination
technique
with
high
spatiotemporal
resolution,
rhythmically
active
medullary
slices
from
;GlyT2
;GAD1
mice.
Stimulation
4
8
during
endogenous
rhythm
prolonged
interburst
interval
phase-dependent
manner
increased
latency
to
burst
initiation
when
bursts
were
evoked
by
stimulation
contrast,
did
not
affect
initiation.
Instead,
photoactivation
duration
decreased
amplitude.
conclude
that
express
both
modulate
delaying
shapes
patterning
altering
Journal of Neuroscience,
Год журнала:
2024,
Номер
44(25), С. e1928232024 - e1928232024
Опубликована: Май 10, 2024
Inhibitory
neurons
embedded
within
mammalian
neural
circuits
shape
breathing,
walking,
and
other
rhythmic
motor
behaviors.
At
the
core
of
circuit
controlling
breathing
is
preBtzinger
Complex
(preBtC),
where
GABAergic
(GAD1/2
+
)
glycinergic
(GlyT2
are
functionally
anatomically
intercalated
among
glutamatergic
Dbx1-derived
(Dbx1
that
generate
inspiratory
drive.
The
roles
these
preBtC
inhibitory
in
remain
unclear.
We
first
characterized
spatial
distribution
molecularly
defined
subpopulations
male
female
neonatal
double
reporter
mice
expressing
either
tdTomato
or
EGFP
GlyT2
,
GAD1
GAD2
neurons.
found
majority
expressed
both
while
a
much
smaller
subpopulation
also
GAD1.
To
determine
functional
role
subpopulations,
we
used
holographic
photostimulation,
patterned
illumination
technique,
rhythmically
active
medullary
slices
from
Dbx1
;GlyT2
;GAD1
sex.
Stimulation
4
8
during
endogenous
rhythm
prolonged
interburst
interval
phase-dependent
manner
increased
latency
to
burst
initiation
when
bursts
were
evoked
by
stimulation
In
contrast,
did
not
affect
initiation.
Instead,
photoactivation
duration
decreased
amplitude.
conclude
/GAD2
modulate
delaying
shapes
patterning
altering
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Сен. 5, 2023
Abstract
Whether
or
not
the
neuron
emits
a
spike
in
response
to
stimulation
by
an
excitatory
current
pulse
is
determined
strength-duration
curve
(SDC)
for
parameters.
The
SDC
dependence
of
minimal
amplitude
required
elicit
spiking
on
either
duration
its
decay
time.
Excitatory
neurons
affect
others
through
pulses
postsynaptic
current.
A
simple
yet
plausible
approximation
time
course
such
alpha
function,
with
linear
rise
at
start
and
exponential
end.
However,
exact
analytical
this
case
hitherto
known,
even
leaky
integrate-
and-fire
(LIF)
neuron,
simplest
model
used
practice.
We
have
obtained
general
equations
LIF
neuron.
Using
Lambert
W
function
—
widely-implemented
special
we
found
stimulated
form
function.
To
compare
results
unified
way,
also
derived
SDCs
(i)
rectangular
pulse,
(ii)
ascending
ramp
(iii)
instantly
rising
exponentially
decaying
pulse.
In
limit
no
leakage,
show
that
reduced
classical
hyperbola
all
considered
cases.