Sevoflurane
has
been
the
most
widely
used
inhaled
anesthetics
with
a
favorable
recovery
profile;
however,
precise
mechanisms
underlying
its
anesthetic
action
are
still
not
completely
understood.
Here
authors
show
that
sevoflurane
activates
cluster
of
urocortin
1
(UCN1
Ketamine
(KET)
and
isoflurane
(ISO)
are
two
widely
used
general
anesthetics,
yet
their
distinct
shared
neurophysiological
mechanisms
remain
elusive.
In
this
study,
we
conducted
a
comparative
analysis
of
the
effects
KET
ISO
on
c-Fos
expression
across
mouse
brain,
utilizing
hierarchical
clustering
c-Fos-based
functional
network
to
evaluate
responses
individual
brain
regions
each
anesthetic.
Our
findings
reveal
that
activates
wide
range
regions,
notably
in
cortical
subcortical
nuclei
involved
sensory,
motor,
emotional,
reward
processing,
with
temporal
association
areas
(TEa)
as
strong
hub,
suggesting
top-down
mechanism
affecting
consciousness
by
primarily
targeting
higher
order
networks.
contrast,
predominantly
influences
hypothalamus,
impacting
neuroendocrine
control,
autonomic
function,
homeostasis,
locus
coeruleus
(LC)
connector
indicating
bottom-up
anesthetic-induced
unconsciousness.
both
activate
sensory
memory
cognition,
motivation,
well
homeostatic
highlighting
various
neural
pathways.
conclusion,
our
results
highlight
but
overlapping
ISO,
enriching
understanding
underlying
anesthesia.
British Journal of Pharmacology,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 10, 2025
Abstract
Background
and
Purpose
The
induction
emergence
of
general
anaesthesia
involve
an
altered
process
states
consciousness,
yet
the
central
nervous
system
mechanisms
remain
inadequately
understood.
ventral
pallidum
(VP)
within
basal
ganglia
is
crucial
in
sleep–wake
modulation.
However,
its
involvement
underlying
neuronal
are
not
well
elucidated.
Experimental
Approach
In
vivo
electrophysiological
recordings
were
conducted
to
examine
changes
activity
different
types
VP
neurons
before
after
sevoflurane
exposure.
Fibre
photometry,
combined
with
electroencephalogram
electromyography
recordings,
was
employed
analyse
during
both
recovery
phases
anaesthesia.
Chemogenetics
implemented
investigate
impact
modulated
on
emergence,
whereas
optogenetics
used
for
real
time
activation
at
depths
Key
Results
Sevoflurane
exposure
reduced
firing
GABAergic
(VP
GABA
)
glutamatergic
glu
neurons,
without
affecting
cholinergic
neurons.
decreased
increased
emergence.
Manipulation
bidirectionally
influenced
duration
Inhibiting
accelerated
induction.
Real
triggered
cortical
behavioural
steady‐state
burst
suppression
ratio
deep
Conclusion
Implications
These
findings
highlight
role
modulating
transitions
between
stages,
providing
valuable
insights
into
sevoflurane‐induced
Ketamine
(KET)
and
isoflurane
(ISO)
are
two
widely
used
general
anesthetics,
yet
their
distinct
shared
neurophysiological
mechanisms
remain
elusive.
In
this
study,
we
conducted
a
comparative
analysis
of
KET
ISO
effects
on
c-Fos
expression
across
the
brain,
utilizing
hierarchical
clustering
c-Fos-based
functional
network
to
evaluate
responses
individual
brain
regions
each
anesthetic.
Our
findings
demonstrate
that
significantly
activates
cortical
subcortical
arousal-promoting
nuclei,
with
temporal
association
areas
(TEa)
serving
as
hub
node,
corroborating
top-down
anesthesia
theory
for
dissociative
anesthesia.
contrast,
nuclei
in
hypothalamus
brainstem,
locus
coeruleus
(LC)
implying
bottom-up
mechanism
anesthetic-induced
unconsciousness.
Notably,
coactivation
arousal-related
analgesia-related,
neuroendocrine-related
(e.g.,
prelimbic
area
(PL)
infralimbic
(ILA),
anterior
paraventricular
nucleus
(aPVT),
Edinger-Westphal
(EW),
(LC),
parabrachial
(PB),
solitary
tract
(NTS)
by
both
anesthetics
underscores
features
such
unconsciousness,
analgesia,
autonomic
regulation,
irrespective
specific
molecular
targets.
conclusion,
our
results
emphasize
actions
while
also
uncovering
commonly
activated
regions,
thus
contributing
advancement
understanding
underlying
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 6, 2023
Abstract
Ketamine
(KET)
and
isoflurane
(ISO)
are
two
widely
used
general
anesthetics,
yet
their
distinct
shared
neurophysiological
mechanisms
remain
elusive.
In
this
study,
we
conducted
a
comparative
analysis
of
the
effects
KET
ISO
on
c-Fos
expression
across
brain,
utilizing
hierarchical
clustering
c-Fos-based
functional
network
to
evaluate
responses
individual
brain
regions
each
anesthetic.
Our
findings
reveal
that
activates
wide
range
regions,
notably
in
cortical
subcortical
nuclei
involved
sensory,
motor,
emotional,
reward
processing,
with
temporal
association
areas
(TEa)
as
strong
hub,
suggesting
top-down
mechanism
affecting
consciousness
by
primarily
targeting
higher-order
networks.
contrast,
predominantly
influences
hypothalamus,
impacting
neuroendocrine
control,
autonomic
function,
homeostasis,
locus
coeruleus
(LC)
connector
indicating
bottom-up
anesthetic-induced
unconsciousness.
both
activate
sensory
memory
cognition,
motivation,
well
homeostatic
highlighting
various
neural
pathways.
conclusion,
our
results
highlight
but
overlapping
ISO,
enriching
understanding
underlying
anesthesia.
