Journal of Neuroscience,
Год журнала:
2022,
Номер
42(38), С. 7244 - 7255
Опубликована: Авг. 15, 2022
Dorsal
raphe
(DR)
5-HT
neurons
regulate
sleep–wake
transitions.
Previous
studies
demonstrated
that
single-unit
activity
of
DR
is
high
during
wakefulness,
decreases
non-rapid
eye
movement
(NREM)
sleep,
and
ceases
rapid
(REM)
sleep.
However,
characteristics
the
population-level
neurons,
which
influence
entire
brain,
are
largely
unknown.
Here,
we
measured
population
activities
in
male
female
mouse
across
cycle
by
ratiometric
fiber
photometry.
We
found
a
slow
oscillatory
compound
intracellular
Ca2+
signals
NREM
The
trough
concave
increased
sleep
progression,
but
always
returned
to
seen
wake
period.
When
reached
minimum
remained
there,
REM
was
initiated.
also
unique
coupling
wideband
EEG
power
fluctuation.
Furthermore,
optogenetic
activation
triggered
EMG
induced
demonstrating
causal
role
neuron
activation.
Optogenetic
inhibition
or
sustained
NREM,
with
an
increase
fluctuation,
pharmacological
silencing
using
selective
serotonin
reuptake
inhibitor
led
decrease
These
inhibitory
manipulations
supported
association
between
propose
not
monotonous
state,
rather
it
contains
dynamic
changes
coincide
neurons.
SIGNIFICANCE
STATEMENT
have
single-cell
neuronal
conditions.
these
well
understood.
monitored
photometry
system
mice
highest
wakefulness
lowest
Surprisingly,
non-REM
decreased
pattern,
coinciding
fluctuations.
fluctuations
persisted
when
silenced
either
interventions
suggesting
two.
Although
did
generate
fluctuations,
provides
evidence
exhibits
at
least
binary
states.
Sleep Medicine Reviews,
Год журнала:
2022,
Номер
62, С. 101592 - 101592
Опубликована: Янв. 21, 2022
Five
decades
ago,
seminal
studies
positioned
the
brainstem
locus
coeruleus
(LC)
norepinephrine
(NE)
system
as
a
key
substrate
for
regulation
of
wakefulness
and
sleep,
this
picture
has
recently
been
elaborated
thanks
to
methodological
advances
in
precise
investigation
experimental
modulation
LC
structure
functions.
This
review
presents
discusses
findings
that
support
major
role
LC-NE
at
different
levels
sleep-wake
organization,
ranging
from
its
involvement
overall
architecture
cycle
associations
with
sleep
microstructure,
while
accounting
intricate
neuroanatomy
surrounding
LC.
Given
particular
position
held
by
being
intersection
dysregulation
initial
pathophysiological
processes
Alzheimer's
disease
(AD),
we
conclude
examining
emerging
opportunities
investigate
mediated
relationships
between
alteration
AD
human
aging.
We
further
propose
several
research
perspectives
could
promising
target
identification
at-risk
individuals
preclinical
stages
AD,
development
novel
preventive
interventions.
Nature Neuroscience,
Год журнала:
2024,
Номер
27(2), С. 249 - 258
Опубликована: Янв. 18, 2024
Abstract
Sleep
interacts
reciprocally
with
immune
system
activity,
but
its
specific
relationship
microglia—the
resident
cells
in
the
brain—remains
poorly
understood.
Here,
we
show
mice
that
microglia
can
regulate
sleep
through
a
mechanism
involving
G
i
-coupled
GPCRs,
intracellular
Ca
2+
signaling
and
suppression
of
norepinephrine
transmission.
Chemogenetic
activation
strongly
promoted
sleep,
whereas
pharmacological
blockade
P2Y12
receptors
decreased
sleep.
Two-photon
imaging
cortex
showed
P2Y12–G
elevated
,
this
elevation
largely
abolished
-induced
increase.
Microglia
level
also
increased
at
natural
wake-to-sleep
transitions,
caused
partly
by
reduced
levels.
Furthermore,
biosensor
significantly
levels,
increasing
adenosine
concentration.
These
findings
indicate
reciprocal
interactions
Continuous
sleep
restores
the
brain
and
body,
whereas
fragmented
harms
cognition
health.
Microarousals
(MAs),
brief
(3-
to
15-s-long)
wake
intrusions
into
sleep,
are
clinical
markers
for
various
disorders.
Recent
rodent
studies
show
that
MAs
during
healthy
non-rapid
eye
movement
(NREM)
driven
by
infraslow
fluctuations
of
noradrenaline
(NA)
in
coordination
with
electrophysiological
rhythms,
vasomotor
activity,
cerebral
blood
volume,
glymphatic
flow.
hence
part
dynamics,
raising
questions
about
their
biological
roles.
We
propose
bolster
NREM
sleep's
benefits
associated
NA
fluctuations,
according
an
inverted
U-shaped
curve.
Weakened
noradrenergic
as
may
occur
neurodegenerative
diseases
or
aids,
reduce
MAs,
exacerbated
caused
stress
fragment
collapse
signaling.
suggest
crucial
restorative
plasticity-promoting
functions
advance
our
insight
normal
pathological
arousal
dynamics
from
sleep.
