Journal of Neuroscience,
Год журнала:
2023,
Номер
43(26), С. 4837 - 4855
Опубликована: Июнь 7, 2023
Decision
making
is
a
complex
cognitive
process
that
recruits
distributed
network
of
brain
regions,
including
the
basolateral
amygdala
(BLA)
and
nucleus
accumbens
shell
(NAcSh).
Recent
work
suggests
communication
between
these
structures,
as
well
activity
cells
expressing
dopamine
(DA)
D2
receptors
(D2R)
in
NAcSh,
are
necessary
for
some
forms
decision
making;
however,
contributions
this
circuit
cell
population
during
under
risk
punishment
unknown.
The
current
experiments
addressed
question
using
circuit-specific
type-specific
optogenetic
approaches
rats
task
involving
punishment.
In
experiment
1,
Long-Evans
received
intra-BLA
injections
halorhodopsin
or
mCherry
(control)
2,
D2-Cre
transgenic
intra-NAcSh
Cre-dependent
mCherry.
Optic
fibers
were
implanted
NAcSh
both
experiments.
Following
training
task,
BLA→NAcSh
D2R-expressing
neurons
optogenetically
inhibited
different
phases
process.
Inhibition
deliberation
(the
time
trial
initiation
choice)
increased
preference
large,
risky
reward
(increased
taking).
Similarly,
inhibition
delivery
punished
taking,
but
only
males.
taking.
contrast,
small,
safe
decreased
These
findings
extend
our
knowledge
neural
dynamics
revealing
sex-dependent
recruitment
dissociable
selective
populations
making.SIGNIFICANCE
STATEMENT
Until
recently,
ability
to
dissect
substrates
(risk
taking)
cell-specific
manner
has
been
limited
by
tools
available
use
rats.
Here,
we
leveraged
temporal
precision
optogenetics,
together
with
rats,
probe
specific
risk-based
making.
Our
reveal
(BLA)→nucleus
(NAcSh)
involved
evaluation
rewards
manner.
Further,
receptor
(D2R)-expressing
make
unique
taking
vary
across
advance
understanding
principles
provide
insight
into
how
may
become
compromised
neuropsychiatric
diseases.
Cell Reports,
Год журнала:
2023,
Номер
42(2), С. 112069 - 112069
Опубликована: Фев. 1, 2023
The
nucleus
accumbens
(NAc)
plays
an
important
role
in
motivation
and
reward
processing.
Recent
studies
suggest
that
different
NAc
subnuclei
differentially
contribute
to
reward-related
behaviors.
However,
how
is
encoded
individual
neurons
remains
unclear.
Using
vivo
single-cell
resolution
calcium
imaging,
we
find
diverse
patterns
of
encoding
the
medial
lateral
shell
subdivision
(NAcMed
NAcLat,
respectively).
Reward
consumption
increases
NAcLat
activity
but
decreases
NAcMed
activity,
albeit
with
high
variability
among
neurons.
heterogeneity
could
be
attributed
differences
their
synaptic
inputs
transcriptional
profiles.
Specific
optogenetic
activation
Nts-positive
promotes
positive
reinforcement,
while
Cartpt-positive
induces
behavior
aversion.
Collectively,
our
study
shows
organizational
subregions
provides
a
framework
for
future
dissection
physiological
pathological
conditions.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Янв. 5, 2023
The
lateral
hypothalamus
(LH)
is
physiologically
critical
in
brain
functions.
LH
also
plays
an
important
role
drug
addiction.
However,
neural
circuits
underlying
involvement
of
addiction
remain
obscure.
In
the
present
study,our
results
showed
that
male
mice,
during
context-induced
expression
morphine
withdrawal
memory,
glutamatergic
neurons
played
role;
dopamine
D1
receptor-expressing
medium
spiny
(D1-MSNs)
projecting
from
core
nucleus
accumbens
(NAcC)
to
were
upstream
circuit
activate
neurons;
D1-MSNs
NAcC
activated
through
inhibiting
local
gamma-aminobutyric
acid
(GABA)
neurons.
These
suggest
disinhibited
by
importantly
contribute
memory.
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.
Neuropsychopharmacology,
Год журнала:
2022,
Номер
48(3), С. 448 - 458
Опубликована: Сен. 7, 2022
Abstract
Addiction-related
compulsion-like
behavior
can
be
modeled
in
rodents
with
drug
self-administration
(SA)
despite
harmful
consequences.
Recent
studies
suggest
that
the
potentiation
of
glutamatergic
transmission
at
orbitofrontal
cortex
(OFC)
to
dorsal
striatum
(DS)
synapses
drives
transition
from
controlled
SA.
However,
timing
induction
this
synaptic
plasticity
remains
elusive.
Here,
mice
were
first
allowed
intravenously
self-administer
cocaine.
When
had
endure
a
risk
electrical
foot
shock,
only
fraction
persevered
cocaine
In
these
persevering
mice,
we
recorded
high
A/N
ratios
(AMPA-R/NMDA-R:
α-amino-3hydroxy-5-methyl-4-isoxazolepropionic
acid
receptor/N-methyl-D-aspartate
receptor)
both
types
spiny
projection
neurons
(i.e.,
D1
and
D2
dopamine
receptor-expressing
SPNs).
By
contrast,
when
prepared
slices
end
acquisition
period,
all
was
D1R-
but
not
D2R-SPNs.
These
results
indicate
SA
emerges
during
punishment
sessions,
where
onto
D2R-SPNs
are
strengthened.
renouncing
individuals,
cocaine-evoked
strengthening
D1R-SPNs
is
lost.
Our
study
thus
reveals
cell-type
specific
sequence
eventually
may
cause
Translational Psychiatry,
Год журнала:
2023,
Номер
13(1)
Опубликована: Янв. 23, 2023
Abstract
Natural
rewards,
such
as
food,
and
sex
are
appetitive
stimuli
available
for
animals
in
their
natural
environment.
Similarly,
addictive
rewards
drugs
of
abuse
possess
strong,
positive
valence,
but
action
relies
on
pharmacological
properties.
Nevertheless,
it
is
believed
that
both
these
kinds
activate
similar
brain
circuitry.
The
present
study
aimed
to
discover
which
parts
the
process
experience
rewards.
To
holistically
address
this
question,
we
used
a
single-cell
whole-brain
imaging
approach
find
patterns
activation
acute
prolonged
sucrose
cocaine
exposure.
We
analyzed
almost
400
structures
created
brain-wide
map
specific,
c-Fos-positive
neurons
engaged
by
Acute
not
exposure
triggered
massive
c-Fos
expression
throughout
brain.
Cocaine
other
hand
potentiated
with
use,
engaging
more
than
treatment.
functional
connectivity
analysis
unraveled
an
increase
modularity
after
initial
types
This
was
increased
repeated
cocaine,
sucrose,
intake.
check
whether
discrepancies
between
processing
can
be
found
cellular
level,
further
studied
nucleus
accumbens,
one
most
strongly
activated
experience.
high
overlap
level
expression.
Electrophysiological
measurements
correlates
synaptic
plasticity
revealed
alike
induce
accumulation
silent
synapses.
These
results
strengthen
hypothesis
accumbens
cause
maladaptive
neuronal
circuitry
typically
processes
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Авг. 8, 2024
Abstract
Powerful
associations
that
link
drugs
of
abuse
with
cues
in
the
drug-paired
environment
often
serve
as
prepotent
relapse
triggers.
Drug-associated
contexts
and
activate
ensembles
nucleus
accumbens
(NAc)
neurons,
including
D1-class
medium
spiny
neurons
(MSNs)
typically
promote,
D2-class
MSNs
oppose,
drug
seeking.
We
found
mice,
cocaine
conditioning
upregulated
transiently
activity-regulated
transcription
factor,
Neuronal
PAS
Domain
Protein
4
(NPAS4),
a
small
subset
NAc
neurons.
The
NPAS4+
ensemble
was
required
for
conditioned
place
preference.
also
observed
NPAS4
functions
within
D2-,
but
not
D1-,
to
support
cocaine-context
cue-induced
cocaine,
sucrose,
Together,
our
data
show
is
essential
itself
D2-MSNs
by
suppressing
drug-induced
counteradaptations
oppose
relapse-related
behaviour.
