Anesthesia & Analgesia,
Год журнала:
2021,
Номер
132(5), С. 1254 - 1264
Опубликована: Апрель 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
A
defining
feature
of
sleep
is
reduced
responsiveness
to
external
stimuli,
but
the
mechanisms
mediating
sensory-evoked
arousal
remain
unclear.
We
hypothesized
that
locus
coeruleus
(LC)
norepinephrine
(NE)
activity
during
mediates
unresponsiveness,
and
its
action
promotes
awakenings.
tested
this
using
electrophysiological,
behavioral,
pharmacological,
optogenetic
techniques
alongside
auditory
stimulation
in
freely
behaving
rats.
found
systemic
reduction
NE
signaling
lowered
probability
sound-evoked
awakenings
(SEAs).
The
level
tonic
LC
anticipated
SEAs.
Optogenetic
activation
promoted
as
evident
sleep-wake
transitions,
EEG
desynchronization,
pupil
dilation.
Minimal
excitation
before
sound
presentation
increased
SEA
probability.
silencing
a
soma-targeted
anion-conducting
channelrhodopsin
(stGtACR2)
suppressed
spiking
constricted
pupils.
Brief
periods
opto-silencing
Thus,
LC-NE
determines
likelihood
awakenings,
constitutes
key
factor
behavioral
unresponsiveness.
Nature Communications,
Год журнала:
2017,
Номер
8(1)
Опубликована: Сен. 25, 2017
Abstract
Sleep
control
is
ascribed
to
a
two-process
model,
widely
accepted
concept
that
posits
homoeostatic
drive
and
circadian
process
as
the
major
sleep-regulating
factors.
Cognitive
emotional
factors
also
influence
sleep–wake
behaviour;
however,
precise
circuit
mechanisms
underlying
their
effects
on
sleep
are
unknown.
Previous
studies
suggest
adenosine
has
role
affecting
behavioural
arousal
in
nucleus
accumbens
(NAc),
brain
area
critical
for
reinforcement
reward.
Here,
we
show
chemogenetic
or
optogenetic
activation
of
excitatory
A
2A
receptor-expressing
indirect
pathway
neurons
core
region
NAc
strongly
induces
slow-wave
sleep.
Chemogenetic
inhibition
prevents
induction,
but
does
not
affect
rebound.
In
addition,
motivational
stimuli
inhibit
activity
ventral
pallidum-projecting
suppress
Our
findings
reveal
prominent
contribution
this
associated
with
motivation.
Frontiers in Neural Circuits,
Год журнала:
2019,
Номер
13
Опубликована: Дек. 5, 2019
The
ventral
tegmental
area
(VTA)
is
best
known
for
its
robust
dopaminergic
projections
to
forebrain
regions
and
their
critical
role
in
regulating
reward,
motivation,
cognition,
aversion.
However,
the
VTA
not
only
made
of
dopamine
(DA)
cells,
as
approximately
35%
cells
are
GABA
neurons.
These
neurons
play
a
dual
role,
provide
both
local
inhibition
DA
long-range
several
distal
brain
regions.
have
increasingly
been
recognized
potent
mediators
reward
aversion
own
right,
well
potential
targets
treatment
addiction,
depression,
other
stress-linked
disorders.
In
this
review,
we
dissect
circuit
architecture,
physiology,
behavioral
roles
suggest
gaps
be
addressed.
Frontiers in Neuroscience,
Год журнала:
2019,
Номер
13
Опубликована: Апрель 24, 2019
Mammals
have
evolved
a
range
of
behavioural
and
neurological
mechanisms
that
coordinate
cycles
thermoregulation
sleep.
Whether
diurnal
or
nocturnal,
sleep
onset
reduction
in
core
temperature
occur
together.
Non-rapid
eye
movement
(NREM)
episodes
are
also
accompanied
by
brain
cooling.
Thermoregulatory
behaviours,
like
nest
building
curling
up,
accompany
this
circadian
decline
preparation
for
sleeping.
This
could
be
matter
simply
comfort
as
animals
seek
warmth
to
compensate
lower
temperatures.
However,
both
humans
other
mammals,
direct
skin
warming
can
shorten
sleep-latency
promote
NREM
We
discuss
the
evidence
body
cooling
more
fundamentally
connected
thermoregulatory
prior
sleep,
form
warm
microclimates
accelerate
directly
through
neuronal
circuits.
Paradoxically,
might
induce
vasodilation
In
way,
seeking
nesting
behaviour
enhance
cycle
activating
specific
circuits
link
initiation
suggest
these
explain
why
is
most
likely
when
at
its
steepest
rate
transitions
decrease
temperature.
connection
may
implications
energy
homeostasis
function
Journal of Neuroscience,
Год журнала:
2016,
Номер
37(5), С. 1352 - 1366
Опубликована: Дек. 30, 2016
The
pedunculopontine
tegmental
(PPT)
nucleus
has
long
been
implicated
in
the
regulation
of
cortical
activity
and
behavioral
states,
including
rapid
eye-movement
(REM)
sleep.
For
example,
electrical
stimulation
PPT
region
during
sleep
leads
to
awakening,
whereas
lesions
cats
reduce
REM
Though
these
effects
have
linked
with
cholinergic
neurons,
also
includes
intermingled
glutamatergic
GABAergic
cell
populations,
precise
roles
cholinergic,
glutamatergic,
groups
regulating
state
remain
unknown.
Using
a
chemogenetic
approach
three
Cre-driver
mouse
lines,
we
found
that
selective
activation
neurons
induced
prolonged
wakefulness,
inhibition
reduced
wakefulness
increased
non-REM
(NREM)
Activation
suppressed
lower-frequency
electroencephalogram
rhythms
NREM
Last,
slightly
These
findings
reveal
differentially
influence
sleep/wake
states.
SIGNIFICANCE
STATEMENT
More
than
40
million
Americans
suffer
from
chronic
disruption,
development
effective
treatments
requires
more
detailed
understanding
neuronal
mechanisms
controlling
arousal.
considered
key
site
for
This
is
mainly
because
contained
nucleus.
However,
contains
likely
contribute
sleep–wake
experiments
present
study
each
distinct
on
behavior,
improving
our
how
regulates
Frontiers in Molecular Neuroscience,
Год журнала:
2020,
Номер
12
Опубликована: Янв. 21, 2020
Dopamine
and
noradrenaline
are
crucial
neuromodulators
controlling
brain
states,
vigilance,
action,
reward,
learning,
memory
processes.
Ventral
tegmental
area
(VTA)
Locus
Coeruleus
(LC)
canonically
described
as
the
main
sources
of
dopamine
(DA)
(NA)
with
dissociate
functions.
A
comparison
diverse
studies
shows
that
these
largely
overlap
in
multiple
domains
such
shared
biosynthetic
pathway
co-release
from
LC
terminals,
convergent
innervations,
non-specificity
receptors
transporters,
intracellular
signaling
pathways.
DA-NA
interactions
mainly
studied
prefrontal
cortex
hippocampus,
yet
it
can
be
extended
to
whole
given
diversity
catecholamine
innervations.
simultaneously
broadcast
both
across
brain.
Here,
we
briefly
review
molecular,
cellular,
physiological
overlaps
between
DA
NA
systems
point
their
functional
implications.
We
suggest
may
function
parallel
facilitate
learning
maintain
states
required
for
normal
cognitive
Various
modules
have
been
targeted
developing
therapeutics.
Understanding
two
is
more
effective
interventions
a
range
neuropsychiatric
conditions.
Annual Review of Neuroscience,
Год журнала:
2019,
Номер
42(1), С. 27 - 46
Опубликована: Янв. 30, 2019
Wakefulness,
rapid
eye
movement
(REM)
sleep,
and
non-rapid
(NREM)
sleep
are
characterized
by
distinct
electroencephalogram
(EEG),
electromyogram
(EMG),
autonomic
profiles.
The
circuit
mechanism
coordinating
these
changes
during
sleep-wake
transitions
remains
poorly
understood.
past
few
years
have
witnessed
progress
in
the
identification
of
REM
NREM
neurons,
which
constitute
highly
distributed
networks
spanning
forebrain,
midbrain,
hindbrain.
Here
we
propose
an
arousal-action
for
control
wakefulness
is
supported
separate
arousal
action
while
neurons
part
central
somatic
motor
circuits.
This
model
well
currently
known
wake
neurons.
It
can
also
account
EEG,
EMG,
profiles
wake,
REM,
states
several
key
features
their
transitions.
intimate
association
between
autonomic/somatic
circuits
suggests
that
a
primary
function
to
suppress
activity.