Mental
and
behavioral
disorders
are
associated
with
extended
period
of
hot
weather
as
found
in
heatwaves,
but
the
underlying
neural
circuit
mechanism
is
poorly
known.
The
posterior
paraventricular
thalamus
(pPVT)
a
hub
for
emotional
processing
receives
inputs
from
hypothalamic
preoptic
area
(POA),
well-recognized
thermoregulation
center.
present
study
was
designed
to
explore
whether
chronic
heat
exposure
leads
aberrant
activities
POA
recipient
pPVT
neurons
subsequent
changes
states.
By
devising
an
air
heating
paradigm
mimicking
condition
heatwaves
utilizing
emotion-related
tests,
viral
track
tracing,
vivo
calcium
recordings,
optogenetic
manipulations
electrophysiological
we
that
3
weeks
led
negative
hyperarousal
states
mice.
receive
monosynaptic
excitatory
inhibitory
innervations
POA.
These
exhibited
persistent
increase
activity
following
exposure,
which
essential
heat-induced
changes.
Notably,
these
were
also
prone
display
stronger
neuronal
anxiety
responses
stressful
situations.
Furthermore,
observed
saturated
neuroplasticity
POA-pPVT
pathway
after
occluded
further
potentiation.
Taken
together,
long-term
aberration
offers
neurobiological
seen
like
heatwaves.
Translational Psychiatry,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: April 8, 2025
Dependence
is
a
hallmark
of
alcohol
use
disorder
characterized
by
excessive
intake
and
withdrawal
symptoms.
The
central
nucleus
the
amygdala
(CeA)
key
brain
structure
underlying
synaptic
behavioral
consequences
ethanol
dependence.
While
accumulating
evidence
suggests
that
astrocytes
regulate
transmission
behavior,
there
limited
understanding
role
play
in
present
study
used
combination
viral
labeling,
super
resolution
confocal
microscopy,
3D
image
analysis,
slice
electrophysiology
to
determine
effects
chronic
intermittent
(CIE)
exposure
on
astrocyte
plasticity
CeA.
During
from
CIE
exposure,
we
observed
increased
GABA
transmission,
an
upregulation
astrocytic
GAT3
levels,
proximity
processes
near
CeA
synapses.
Furthermore,
levels
were
positively
associated
with
voluntary
drinking
dependent
rats.
Slice
confirmed
was
functional,
as
unmasked
GAT3-sensitive
tonic
current
A
causal
for
dependence
assessed
using
viral-mediated
overexpression
knockdown
approaches.
However,
or
had
no
effect
somatic
symptoms,
dependence-escalated
intake,
aversion-resistant
drinking,
post-dependent
male
female
Moreover,
intra-CeA
pharmacological
inhibition
did
not
alter
drinking.
Together,
these
findings
indicate
induces
GABAergic
dysregulation
changes
do
appear
be
necessary
related
phenotypes
Mental
and
behavioral
disorders
are
associated
with
extended
period
of
hot
weather
as
found
in
heatwaves,
but
the
underlying
neural
circuit
mechanism
is
poorly
known.
The
posterior
paraventricular
thalamus
(pPVT)
a
hub
for
emotional
processing
receives
inputs
from
hypothalamic
preoptic
area
(POA),
well-recognized
thermoregulation
center.
present
study
was
designed
to
explore
whether
chronic
heat
exposure
leads
aberrant
activities
POA
recipient
pPVT
neurons
subsequent
changes
states.
By
devising
an
air
heating
paradigm
mimicking
condition
heatwaves
utilizing
emotion-related
tests,
viral
track
tracing,
vivo
calcium
recordings,
optogenetic
manipulations
electrophysiological
we
that
3
weeks
led
negative
valence
hyperarousal
states
mice.
receive
monosynaptic
excitatory
inhibitory
innervations
POA.
These
exhibited
persistent
increase
activity
following
exposure,
which
essential
heat-induced
changes.
Notably,
these
were
also
prone
display
stronger
neuronal
anxiety
responses
stressful
situations.
Furthermore,
observed
saturated
neuroplasticity
POA-pPVT
pathway
after
occluded
further
potentiation.
Taken
together,
long-term
aberration
offers
neurobiological
seen
periods
like
heatwaves.
Mental
and
behavioral
disorders
are
associated
with
extended
period
of
hot
weather
as
found
in
heatwaves,
but
the
underlying
neural
circuit
mechanism
remains
poorly
known.
The
posterior
paraventricular
thalamus
(pPVT)
is
a
hub
for
emotional
processing
receives
inputs
from
hypothalamic
preoptic
area
(POA),
well-recognized
thermoregulation
center.
present
study
was
designed
to
explore
whether
chronic
heat
exposure
leads
aberrant
activities
POA
recipient
pPVT
neurons
subsequent
changes
states.
By
devising
an
air
heating
paradigm
mimicking
condition
heatwaves
utilizing
emotion-related
tests,
viral
tract
tracing,
vivo
calcium
recordings,
optogenetic
manipulations,
electrophysiological
we
that
3
weeks
led
negative
valence
hyperarousal
states
mice.
receive
monosynaptic
excitatory
inhibitory
innervations
POA.
These
exhibited
persistent
increase
activity
following
exposure,
which
essential
heat-induced
changes.
Notably,
these
were
also
prone
display
stronger
neuronal
anxiety
responses
stressful
situations.
Furthermore,
observed
saturated
neuroplasticity
POA-pPVT
pathway
after
occluded
further
potentiation.
Taken
together,
long-term
aberration
offers
neurobiological
seen
periods
like
heatwaves.
JCI Insight,
Journal Year:
2025,
Volume and Issue:
10(8)
Published: April 21, 2025
The
FDA-approved
phosphodiesterase
type
4
(PDE4)
inhibitor,
apremilast,
has
been
recently
investigated
as
a
pharmacotherapy
for
alcohol
use
disorder
(AUD)
with
promising
efficacy
in
rodent
models
and
humans.
However,
apremilast's
effects
on
mechanical
allodynia
associated
AUD
well
distinct
responses
of
this
drug
between
males
females
are
understudied.
present
study
examined
the
behavioral
electrophysiological
apremilast
Marchigian
Sardinian
alcohol-preferring
(msP)
rats
their
Wistar
counterparts.
We
used
2-bottle
choice
(2-BC)
drinking
procedure
tested
sensitivity
across
our
regimen.
Spontaneous
inhibitory
GABA-mediated
postsynaptic
currents
from
central
nucleus
amygdala
(CeA)
following
application
were
subset
using
ex
vivo
electrophysiology.
Transcript
levels
Pde4a
or
-4b
subtypes
assessed
modulation
by
alcohol.
Apremilast
reduced
both
strains
rats.
immediately
after
drinking,
persisting
into
early
late
abstinence.
increased
GABAergic
transmission
CeA
slices
alcohol-exposed
Wistars
but
not
msP
rats,
suggesting
neuroadaptations
msPs
excessive
allodynia.
Pde4
subtype
transcript
These
results
suggest
that
alleviates
co-occurring
pain
sensitivity,
they
further
confirm
PDE4's
role
pain-associated
AUD.
Mental
and
behavioral
disorders
are
associated
with
extended
period
of
hot
weather
as
found
in
heatwaves,
but
the
underlying
neural
circuit
mechanism
is
poorly
known.
The
posterior
paraventricular
thalamus
(pPVT)
a
hub
for
emotional
processing
receives
inputs
from
hypothalamic
preoptic
area
(POA),
well-recognized
thermoregulation
center.
present
study
was
designed
to
explore
whether
chronic
heat
exposure
leads
aberrant
activities
POA
recipient
pPVT
neurons
subsequent
changes
states.
By
devising
an
air
heating
paradigm
mimicking
condition
heatwaves
utilizing
emotion-related
tests,
viral
track
tracing,
vivo
calcium
recordings,
optogenetic
manipulations
electrophysiological
we
that
3
weeks
led
negative
valence
hyperarousal
states
mice.
receive
monosynaptic
excitatory
inhibitory
innervations
POA.
These
exhibited
persistent
increase
activity
following
exposure,
which
essential
heat-induced
changes.
Notably,
these
were
also
prone
display
stronger
neuronal
anxiety
responses
stressful
situations.
Furthermore,
observed
saturated
neuroplasticity
POA-pPVT
pathway
after
occluded
further
potentiation.
Taken
together,
long-term
aberration
offers
neurobiological
seen
periods
like
heatwaves.