Proceedings of the National Academy of Sciences,
Journal Year:
2022,
Volume and Issue:
119(45)
Published: Nov. 4, 2022
In
our
daily
life,
we
are
exposed
to
uncontrollable
and
stressful
events
that
disrupt
sleep.
However,
the
underlying
neural
mechanisms
deteriorating
quality
of
non-rapid
eye
movement
sleep
(NREMs)
REM
largely
unknown.
Here,
show
in
mice
acute
psychosocial
stress
disrupts
by
increasing
brief
arousals
(microarousals
[MAs]),
reducing
spindles,
impairing
infraslow
oscillations
spindle
band
electroencephalogram
during
NREMs,
while
REMs.
This
poor
was
reflected
an
increased
number
calcium
transients
activity
noradrenergic
(NE)
neurons
locus
coeruleus
(LC)
NREMs.
Opto-
chemogenetic
LC-NE
activation
naïve
is
sufficient
change
microarchitecture
similar
stress.
Conversely,
chemogenetically
inhibiting
reduced
MAs
NREMs
normalized
their
after
Specifically
projecting
preoptic
area
hypothalamus
(POA)
decreased
enhanced
spindles
REMs
Optrode
recordings
revealed
stimulating
fibers
POA
indeed
suppressed
spiking
activated
inactivated
MAs.
Our
findings
reveal
changes
dynamics
stress-regulatory
negatively
affect
quality,
partially
through
interaction
with
POA.
Journal of Neuroscience,
Journal Year:
2019,
Volume and Issue:
39(42), P. 8239 - 8249
Published: Oct. 16, 2019
The
locus
coeruleus
(LC)
is
a
seemingly
singular
and
compact
neuromodulatory
nucleus
that
prominent
component
of
disparate
theories
brain
function
due
to
its
broad
noradrenergic
projections
throughout
the
CNS.
As
diffuse
system,
noradrenaline
affects
learning
decision
making,
control
sleep
wakefulness,
sensory
salience
including
pain,
physiology
correlated
forebrain
activity
(ensembles
networks)
hemodynamic
responses.
However,
our
understanding
LC
undergoing
dramatic
shift
application
state-of-the-art
methods
reveal
many
modules
provide
targeted
neuromodulation.
Here,
we
review
evidence
supporting
modular
based
on
multiple
levels
observation
(developmental,
genetic,
molecular,
anatomical,
neurophysiological).
We
suggest
concept
as
and,
alongside
it,
role
in
diverse
must
be
reconsidered.
Journal of Neuroscience,
Journal Year:
2020,
Volume and Issue:
41(2), P. 320 - 330
Published: Nov. 19, 2020
Vagus
nerve
stimulation
(VNS)
is
widely
used
to
treat
drug-resistant
epilepsy
and
depression.
While
the
precise
mechanisms
mediating
its
long-term
therapeutic
effects
are
not
fully
resolved,
they
likely
involve
locus
coeruleus
(LC)
via
nucleus
of
solitary
tract,
which
receives
afferent
vagal
inputs.
In
rats,
VNS
elevates
LC
firing
forebrain
noradrenaline
levels,
whereas
lesions
suppress
efficacy.
Noninvasive
transcutaneous
(tVNS)
uses
electrical
that
targets
auricular
branch
vagus
at
cymba
conchae
ear.
However,
extent
tVNS
mimics
remains
unclear.
Here,
we
investigated
short-term
in
healthy
human
male
volunteers
(
n
=
24),
using
high-density
EEG
pupillometry
during
visual
fixation
rest.
We
compared
short
(3.4
s)
trials
sham
earlobe
(far
from
branch)
control
for
somatosensory
stimulation.
Although
did
differ
subjective
intensity
ratings,
led
robust
pupil
dilation
(peaking
4–5
s
after
trial
onset)
was
significantly
higher
than
following
further
quantified,
parallel
factor
analysis,
how
modulates
idle
occipital
alpha
(8–13Hz)
activity
identified
each
participant.
found
greater
attenuation
oscillations
by
This
demonstrates
reliably
induces
pupillary
markers
arousal
beyond
stimulation,
thus
supporting
hypothesis
other
arousal-promoting
neuromodulatory
signaling,
invasive
VNS.
SIGNIFICANCE
STATEMENT
Current
noninvasive
brain
techniques
mostly
confined
modulating
cortical
activity,
as
typical
with
transcranial
magnetic
or
direct/alternating
current
Transcutaneous
has
been
proposed
stimulate
subcortical
nuclei,
though
previous
studies
yielded
inconsistent
results.
Here
show
pulses
naive
induced
transient
oscillations.
These
line
established
on
coeruleus–noradrenaline
support
Therefore,
can
be
a
tool
studying
endogenous
signaling
affects
cognition,
including
perception,
attention,
memory,
decision-making;
also
developing
novel
clinical
applications.
Current Biology,
Journal Year:
2021,
Volume and Issue:
31(22), P. 5009 - 5023.e7
Published: Oct. 14, 2021
To
understand
what
makes
sleep
vulnerable
in
disease,
it
is
useful
to
look
at
how
wake-promoting
mechanisms
affect
healthy
sleep.
Wake-promoting
neuronal
activity
inhibited
during
non-rapid-eye-movement
(NREMS).
However,
sensory
vigilance
persists
NREMS
animals
and
humans,
suggesting
that
wake
promotion
could
remain
functional.
Here,
we
demonstrate
consolidated
mouse
a
brain
state
with
recurrent
fluctuations
of
the
neurotransmitter
noradrenaline
on
∼50-s
timescale
thalamus.
These
occurred
around
mean
levels
greater
than
ones
quiet
wakefulness,
while
(NA)
declined
steeply
REMS.
They
coincided
clustering
spindle
rhythms
forebrain
heart-rate
variations,
both
which
are
correlates
arousability.
We
addressed
origins
these
by
using
closed-loop
optogenetic
locus
coeruleus
(LC)
activation
or
inhibition
timed
moments
low
high
NREMS.
suppress,
lock,
entrain
sleep-spindle
fore-
hindbrain-projecting
LC
neurons
show
coordinated
infraslow
variations
natural
Noradrenergic
modulation
thalamic,
but
not
cortical,
circuits
was
required
for
involved
NA
release
into
primary
reticular
thalamic
nuclei
activated
α1-
β-adrenergic
receptors
cause
slowly
decaying
membrane
depolarizations.
signaling
constitutes
vigilance-promoting
mechanism
renders
mammalian
disruption
close-to-minute
through
sustaining
thalamocortical
autonomic
arousability.Video
abstracthttps://www.cell.com/cms/asset/ab9ec3b8-a3f1-470e-8a9c-a2d6ebebc742/mmc3.mp4Loading
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Frontiers in Neural Circuits,
Journal Year:
2021,
Volume and Issue:
15
Published: June 7, 2021
The
locus
coeruleus
(LC),
a
small
brainstem
nucleus,
is
the
primary
source
of
neuromodulator
norepinephrine
(NE)
in
brain.
LC
receives
input
from
widespread
brain
regions,
and
projects
throughout
forebrain,
brainstem,
cerebellum,
spinal
cord.
neurons
release
NE
to
control
arousal,
but
also
context
variety
sensory-motor
behavioral
functions.
Despite
its
brain-wide
effects,
much
about
role
LC-NE
behavior
circuits
controlling
activity
unknown.
New
evidence
suggests
that
modular
input-output
organization
could
enable
transient,
task-specific
modulation
distinct
regions.
Future
work
must
further
assess
whether
this
spatial
modularity
coincides
with
functional
differences
subpopulations
acting
at
specific
times,
how
such
spatiotemporal
specificity
might
influence
learned
behaviors.
Here,
we
summarize
state
field
present
new
ideas
on
Anesthesia & Analgesia,
Journal Year:
2021,
Volume and Issue:
132(5), P. 1254 - 1264
Published: April 14, 2021
General
anesthesia
is
characterized
by
loss
of
consciousness,
amnesia,
analgesia,
and
immobility.
Important
molecular
targets
general
anesthetics
have
been
identified,
but
the
neural
circuits
underlying
discrete
end
points
remain
incompletely
understood.
natural
sleep
share
common
feature
reversible
unconsciousness,
recent
developments
in
neuroscience
enabled
elegant
studies
that
investigate
brain
nuclei
this
important
point.
A
approach
to
measure
cortical
activity
across
electroencephalogram
(EEG),
which
can
reflect
local
neuronal
as
well
connectivity
among
regions.
The
EEG
oscillations
observed
during
depend
greatly
on
anesthetic
agent
dosing,
only
some
resemble
those
sleep.
For
example,
dexmedetomidine
sedation
are
similar
stage
2
nonrapid
eye
movement
(NREM)
sleep,
high
doses
propofol
ether
produce
burst
suppression,
a
pattern
never
Sleep
primarily
driven
withdrawal
subcortical
excitation
cortex,
directly
act
at
both
targets.
While
appear
activate
specific
sleep-active
regions
induce
not
all
play
significant
role
anesthesia.
Anesthetics
also
inhibit
neurons,
it
likely
each
class
drugs
produces
distinct
combination
effects
lead
unconsciousness.
Conversely,
arousal
promote
wakefulness
involved
emergence
activating
them
accelerate
recovery
consciousness.
Modern
techniques
enable
manipulation
led
new
insights
into
circuitry
In
coming
years,
we
will
continue
better
understand
mechanisms
generate
these
states
