bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 7, 2023
SUMMARY
The
successful
pursuit
of
goals
requires
the
coordinated
execution
and
termination
actions
that
lead
to
positive
outcomes.
This
process
is
thought
rely
on
motivational
states
are
guided
by
internal
drivers,
such
as
hunger
or
fear.
However,
mechanisms
which
brain
tracks
shape
instrumental
not
fully
understood.
paraventricular
nucleus
thalamus
(PVT)
a
midline
thalamic
shapes
motivated
behaviors
via
its
projections
accumbens
(NAc)
1–8
monitors
state
interoceptive
inputs
from
hypothalamus
brainstem
3,9–14
.
Recent
studies
indicate
PVT
can
be
subdivided
into
two
major
neuronal
subpopulations,
namely
D2(+)
D2(–)
,
differ
in
genetic
identity,
functionality,
anatomical
connectivity
other
regions,
including
NAc
4,15,16
In
this
study,
we
used
fiber
photometry
investigate
vivo
dynamics
these
distinct
types
mice
performing
reward
foraging-like
behavioral
task.
We
discovered
D2(−)
neurons
encode
goal-oriented
actions,
respectively.
Furthermore,
activity
population
mirrored
motivation
parameters
vigor
satiety.
Similarly,
neurons,
also
some
but
much
lesser
extent.
Importantly,
features
were
largely
preserved
when
was
selectively
assessed.
Collectively,
our
results
highlight
existence
parallel
thalamo-striatal
participate
dynamic
regulation
goal
pursuits
provide
insight
actions.
American Journal of Psychiatry,
Год журнала:
2025,
Номер
182(2), С. 198 - 208
Опубликована: Янв. 15, 2025
The
behavioral
and
diagnostic
heterogeneity
within
the
opioid
use
disorder
(OUD)
diagnosis
is
not
readily
captured
in
current
animal
models,
limiting
translational
relevance
of
mechanistic
research
that
conducted
experimental
animals.
authors
hypothesized
a
nonlinear
clustering
OUD-like
traits
would
capture
population
yield
subpopulations
OUD
vulnerable
rats
with
distinct
neurocircuit
profiles.
Over
900
male
female
heterogeneous
stock
rats,
line
capturing
genetic
present
humans,
were
assessed
for
several
measures
heroin
rewarded
non-rewarded
seeking
behaviors.
A
stochastic
block
model
analysis
was
used
to
assign
vulnerable,
intermediate,
resilient
clusters.
Additional
tests
circuit
analyses
using
c-fos
protein
activation
on
subpopulations.
exhibited
greater
taking
behaviors
relative
those
intermediate
Akin
human
diagnosis,
further
rat
subclustering
revealed
different
combinations
traits,
including
sex
differences.
Lastly,
cue-induced
neuronal
patterns
differed
between
phenotypes.
Behavioral
differences
recapitulated
circuitry
activation,
preferential
engagement
extended
amygdala
stress
males
cortico-striatal
drug
cue-seeking
females.
Using
approach
reflective
diagnosis.
vulnerability
resiliency
associated
patterns,
posing
this
as
tool
assessing
neurobiological
mechanisms
underpinning
OUD.
Current Biology,
Год журнала:
2024,
Номер
34(7), С. 1549 - 1560.e3
Опубликована: Март 7, 2024
The
successful
pursuit
of
goals
requires
the
coordinated
execution
and
termination
actions
that
lead
to
positive
outcomes.
This
process
relies
on
motivational
states
are
guided
by
internal
drivers,
such
as
hunger
or
fear.
However,
mechanisms
which
brain
tracks
shape
instrumental
not
fully
understood.
paraventricular
nucleus
thalamus
(PVT)
is
a
midline
thalamic
shapes
motivated
behaviors
via
its
projections
accumbens
(NAc)
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 7, 2025
Neuromodulatory
signaling
is
poised
to
serve
as
a
neural
mechanism
for
gain
control,
acting
crucial
tuning
factor
influence
neuronal
activity
by
dynamically
shaping
excitatory
and
inhibitory
fast
neurotransmission.
The
endocannabinoid
(eCB)
system,
the
most
widely
expressed
neuromodulatory
system
in
mammalian
brain,
known
filter
inputs
through
retrograde,
pre-synaptic
action.
However,
whether
eCBs
exert
retrograde
control
ultimately
facilitate
reward-seeking
behaviors
freely
moving
mammals
not
established.
Using
suite
of
vivo
physiological,
imaging,
genetic
machine
learning-based
approaches,
we
report
fundamental
role
controlling
behavioral
engagement
behavior
defined
thalamo-striatal
circuit.
Frontiers in Behavioral Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Авг. 9, 2024
The
nucleus
accumbens
(NAc),
a
central
component
of
the
brain's
reward
circuitry,
has
been
implicated
in
wide
range
behaviors
and
emotional
states.
Emerging
evidence,
primarily
drawing
from
recent
rodent
studies,
suggests
that
function
NAc
aversion
processing
is
multifaceted.
Prolonged
stress
or
drug
use
induces
maladaptive
neuronal
which
results
pathological
conditions.
This
review
aims
to
provide
comprehensive
up-to-date
insights
on
role
motivated
behavior
regulation
highlights
areas
demand
further
in-depth
analysis.
It
synthesizes
latest
findings
how
distinct
populations
pathways
contribute
opposite
valences.
examines
neuromodulators,
especially
monoamines,
influence
NAc's
control
over
various
motivational
Furthermore,
it
delves
into
complex
underlying
mechanisms
psychiatric
disorders
such
as
addiction
depression
evaluates
prospective
interventions
restore
functionality.
Opioid
use
disorder
is
marked
by
a
progressive
change
in
the
motivation
to
administer
drug
even
presence
of
negative
consequences.
After
long
periods
abstinence,
urge
return
taking
intensifies
over
time,
known
as
incubation
craving.
Conditioned
responses
drug-related
stimuli,
can
acquire
motivational
properties
and
exert
control
motivated
behaviors
leading
relapse.
Although,
preclinical
data
suggest
that
behavioral
expression
opioid
similar
between
male
female
rodents,
we
do
not
have
conclusive
results
on
sex
differences
craving
relapse
across
abstinence
periods.
Here,
investigated
effects
from
oxycodone
self-administration
neurotransmission
paraventricular
thalamus
(PVT)
nucleus
accumbens
shell
(NAcSh)
pathway
rats.
Using
optogenetics
ex
vivo
electrophysiology,
assessed
synaptic
strength
glutamate
release
probability
this
pathway,
well
NAcSh
medium
spiny
neurons
(MSN)
intrinsic
excitability,
slices
rats
which
were
subjected
either
1
(acute)
or
14
(prolonged)
days
forced
after
self-administration.
Our
revealed
no
somatic
withdrawal
symptoms
following
acute
abstinence.
However,
found
sex-specific
enhancement
cue-induced
prolonged,
but
acute,
self-administration,
with
females
exhibiting
higher
rates.
Notably,
prolonged
led
increases
at
PVT-NAcSh
inputs
compared
saline
controls
both
sexes,
was
observed
Thus,
time-dependent
increase
These
findings
leads
significant
changes,
contributing
heightened
vulnerability,
highlighting
need
for
targeted
therapeutic
strategies
disorder.
Opioid
use
disorder
is
marked
by
a
progressive
change
in
the
motivation
to
administer
drug
even
presence
of
negative
consequences.
After
long
periods
abstinence,
urge
return
taking
intensifies
over
time,
known
as
incubation
craving.
Conditioned
responses
drug-related
stimuli,
can
acquire
motivational
properties
and
exert
control
motivated
behaviors
leading
relapse.
Although,
preclinical
data
suggest
that
behavioral
expression
opioid
similar
between
male
female
rodents,
we
do
not
have
conclusive
results
on
sex
differences
craving
relapse
across
abstinence
periods.
Here,
investigated
effects
from
oxycodone
self-administration
neurotransmission
paraventricular
thalamus
(PVT)
nucleus
accumbens
shell
(NAcSh)
pathway
rats.
Using
optogenetics
ex
vivo
electrophysiology,
assessed
synaptic
strength
glutamate
release
probability
this
pathway,
well
NAcSh
medium
spiny
neurons
(MSN)
intrinsic
excitability,
slices
rats
which
were
subjected
either
1
(acute)
or
14
(prolonged)
days
forced
after
self-administration.
Our
revealed
no
somatic
withdrawal
symptoms
following
acute
abstinence.
However,
found
sex-specific
enhancement
cue-induced
prolonged,
but
acute,
self-administration,
with
females
exhibiting
higher
rates.
Notably,
prolonged
led
increases
at
PVT-NAcSh
inputs
compared
saline
controls
both
sexes,
was
observed
Thus,
time-dependent
increase
These
findings
leads
significant
changes,
contributing
heightened
vulnerability,
highlighting
need
for
targeted
therapeutic
strategies
disorder.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 13, 2025
Understanding
how
the
brain
integrates
internal
physiological
states
with
external
sensory
cues
to
guide
behavior
is
a
fundamental
question
in
neuroscience.
This
process
relies
on
interoceptive
predictions-internal
models
that
anticipate
changes
body's
state
based
inputs
and
prior
experiences.
Despite
recent
advances
identifying
neural
substrates
of
predictions,
precise
neuronal
circuits
involved
remain
elusive.
In
our
study,
we
demonstrate
Dopamine
2
Receptor
(D2+)
expressing
neurons
paraventricular
nucleus
thalamus
(PVT)
play
key
roles
interoception
predictions.
Specifically,
these
are
engaged
behaviors
leading
physiologically
relevant
outcomes,
their
activity
highly
dependent
mice
expected
outcome.
Furthermore,
show
chronic
inhibition
PVT
D2+
impairs
long-term
performance
interoceptive-guided
motivated
behavior.
Collectively,
findings
provide
insights
into
role
learning
updating
state-dependent
by
integrating
past
experiences
current
conditions
optimize
goal-directed
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 23, 2024
The
behavioral
and
diagnostic
heterogeneity
within
human
opioid
use
disorder
(OUD)
diagnosis
is
not
readily
captured
in
current
animal
models,
limiting
translational
relevance
of
the
mechanistic
research
that
conducted
experimental
animals.
We
hypothesize
a
non-linear
clustering
OUD-like
traits
will
capture
population
yield
subpopulations
OUD
vulnerable
rats
with
distinct
neurocircuit
profiles.