bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 30, 2024
Relapse
represents
a
consistent
clinical
problem
for
individuals
with
substance
use
disorder.
In
the
incubation
of
craving
model
persistent
and
relapse,
cue-induced
drug
seeking
progressively
intensifies
or
'incubates'
during
first
weeks
abstinence
from
self-administration
then
remains
high
months.
Previously,
we
others
have
demonstrated
that
expression
incubated
cocaine
requires
strengthening
excitatory
synaptic
transmission
in
nucleus
accumbens
core
(NAcc).
However,
despite
importance
dopaminergic
signaling
NAcc
motivated
behavior,
little
is
known
about
role
dopamine
(DA)
plays
craving.
Here
used
fiber
photometry
to
measure
DA
transients
male
female
rats
tests
conducted
early
self-administration,
prior
incubation,
late
abstinence,
after
has
plateaued.
We
observed
time-locked
responding
but
their
magnitude
did
not
differ
significantly
when
measured
versus
tests.
Next,
tested
functional
these
by
injecting
receptor
antagonists
into
just
before
test.
Blockade
either
D1
D2
receptors
reduced
incubation.
found
no
main
effect
sex
our
experiments.
These
results
suggest
contributes
emergence
this
reflects
changes
postsynaptic
responsiveness
rather
than
presynaptic
alterations.
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Сен. 16, 2024
Survival
relies
on
an
organism's
intrinsic
ability
to
instinctively
react
stimuli
such
as
food,
water,
and
threats,
ensuring
the
fundamental
feed,
drink,
avoid
danger
even
in
absence
of
prior
experience.
These
natural,
unconditioned
can
also
facilitate
associative
learning,
where
pairing
them
consistently
with
neutral
cues
will
elicit
responses
these
cues.
Threat
conditioning,
a
well-explored
form
commonly
employs
painful
electric
shocks,
mimicking
injury,
stimuli.
It
remains
elusive
whether
actual
injury
or
pain
is
necessary
for
effective
threat
harm
sufficient.
Approaching
predators
create
looming
shadows
sounds,
triggering
strong
innate
defensive
like
escape
freezing.
This
study
investigates
visual
induce
learned
freezing
conditioned
stimulus
male
rats.
Surprisingly,
tone
only
weakly
evokes
responses,
contrast
observed
when
replaced
by
shock.
dissociation
sheds
light
boundaries
thereby
impacting
our
comprehension
learning
processes
strategies.
Striatal
dopamine
(DA)
release
regulates
reward-related
learning
and
behavioural
activation
is
believed
to
consist
of
a
short-lived
phasic
continuous
tonic
component.
Here,
we
build
three-dimensional
model
extracellular
DA
dynamics
in
dorsal
(DS)
ventral
striatum
(VS)
that
include
tens
thousands
sites.
The
predicts
rapid
DS
with
little-to-no
basal
DA,
much
slower
the
VS
enabling
build-up
level.
These
regional
differences
do
not
primarily
reflect
different
phenomena
but
rather
arise
from
differential
transporter
(DAT)
activity.
Interestingly,
our
simulations
posit
prevalent
nanoclustering
DAT
as
possible
regulator
this
Receptor
binding
show
D1
receptor
occupancy
follows
concentration
millisecond
delay,
while
D2
receptors
integrate
signal
over
seconds.
Summarized,
distills
recent
experimental
observations
into
computational
framework
challenge
prevailing
paradigms
striatal
signalling.
Striatal
dopamine
(DA)
release
regulates
reward-related
learning
and
behavioural
activation
is
believed
to
consist
of
a
short-lived
phasic
continuous
tonic
component.
Here,
we
build
three-dimensional
model
extracellular
DA
dynamics
in
dorsal
(DS)
ventral
striatum
(VS)
that
include
tens
thousands
sites.
The
predicts
rapid
DS
with
little-to-no
basal
DA,
much
slower
the
VS
enabling
build-up
level.
These
regional
differences
do
not
primarily
reflect
different
phenomena
but
rather
arise
from
differential
transporter
(DAT)
activity.
Interestingly,
our
simulations
posit
prevalent
nanoclustering
DAT
as
possible
regulator
this
Receptor
binding
show
D1
receptor
occupancy
follows
concentration
millisecond
delay,
while
D2
receptors
integrate
signal
over
seconds.
Summarized,
distills
recent
experimental
observations
into
computational
framework
challenge
prevailing
paradigms
striatal
signalling.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 13, 2025
Abstract
Extinction-reinstatement
paradigms
have
been
used
to
study
reward
seeking
for
both
food
and
drug
rewards.
The
nucleus
accumbens
is
of
particular
interest
in
reinstatement
due
its
ability
energize
motivated
behavior.
Indeed,
previous
work
has
demonstrated
that
suppression
neuronal
activity
or
dopaminergic
signaling
the
reduces
seeking.
In
this
study,
we
sought
further
establish
a
connection
between
glutamatergic
input,
measured
by
proxy
via
genetically
encoded
calcium
indicator,
dopamine
(DA)
tone,
simultaneously
with
red-shifted
DA
biosensor.
We
performed
sensor
multiplexing
core
classic
extinction-reinstatement
paradigm
reward.
detected
transients
changed
magnitude
and/or
temporally
shifted
over
course
self-administration
training.
our
traces
observed
decrease
from
baseline
time-locked
lever
press
reward,
which
became
more
prominent
Both
patterns
were
reduced
first
session
extinction
no
deflections
either
last
session.
When
recorded
during
tests,
bootstrapping
analysis
response
when
was
primed
cue
pellet+cue
presentation,
while
reinstatement.
These
data
role
represent
attempt
record
two
an
task.
Frontiers in Cellular Neuroscience,
Год журнала:
2025,
Номер
19
Опубликована: Апрель 15, 2025
The
dopaminergic
modulation
of
striatal
circuit
function
remains
intensely
studied
and
debated.
Nevertheless,
a
prevalent
view
is
that
dopamine
serves
important
roles
in
both
reinforcement
learning
the
performance
movements,
two
highly
distinct
processes.
But
this
dichotomy
has
led
to
longstanding
problem
how
interpret
functional
consequences
particular
signal—is
it
learn
or
move?
In
order
explore
ambiguity
approach
possible
resolution,
review
examines
key
evidence
for
dopamine’s
role
movement.
As
part
discussion,
we
consider
recent
body
views
common
dichotomous
perspective
through
more
nuanced
lens,
by
suggesting
comparatively
limited
contribution
This
concept,
which
refer
as
primacy
hypothesis,
offers
unified
conceptual
framework
understanding
function.
Dopaminergic
neurons
influence
diverse
behaviors
with
varied
firing
patterns,
yet
the
precise
mechanisms
remain
unclear.
We
introduce
a
multiplexed
genetically
encoded
sensor–based
imaging
and
voltammetry
method
to
simultaneously
record
synaptic,
perisynaptic,
extrasynaptic
dopaminergic
transmission
at
mouse
central
neurons.
Using
this
alongside
image
analysis
program,
we
found
that
heterogeneous
patterns
create
various
modes,
encoding
frequency,
number,
synchrony
of
pulses
using
neurotransmitter
quantity,
releasing
synapse
count,
synaptic
and/or
volume
transmission.
Under
both
tonic
low-frequency
phasic
activities,
transporters
effectively
reuptake
dopamine
perisynaptic
sites,
confining
within
clefts
mediate
In
contrast,
under
high-frequency,
particularly
synchronized
activity
or
transporter
inhibition,
released
may
overwhelm
transporters,
escaping
from
via
one
three
outlet
channels,
triggering
Our
study
illuminates
collaborative
mechanism
enclosures,
properties,
defines
coding
principles
pattern–dependent
modes.
IEEE Sensors Journal,
Год журнала:
2023,
Номер
23(15), С. 16456 - 16466
Опубликована: Июнь 19, 2023
Neurotransmitters
are
small
chemical
signaling
molecules
crucial
for
the
proper
function
of
nervous
system.
The
dysregulation
neurotransmitters
results
in
several
mental
disorders
like
Parkinson's
and
Alzheimer's
diseases,
schizophrenia,
conditions
such
as
depression
addiction.
These
present
at
low
concentrations,
obtaining
information
about
these
molecules'
levels
is
vital.
Moreover,
neurotransmitter
monitoring
system
remains
challenging
due
to
its
concentrations
rapid
response.
Electrochemical
detection
continues
garner
significant
attention
an
attractive
technique
facile
nature,
high
sensitivity,
cost-effectiveness.
electroactive
materials
electrochemical
sensors
heart
this
sensing
technology.
Although
multiple
nanomaterials
have
been
explored
active
components
detecting
neurotransmitters,
MXenes
gaining
neurotransmitters.
This
review
aims
discuss
use
their
composites
describe
various
MXene
based
on
nature
composite
viz
pristine
functionalized,
carbon
nanomaterial,
polymer,
metal
nanoparticle,
transition
dichalcogenide
(TMDC)
composites,
define
future
directions
leveraging
properties
early-stage
neurological
diseases
originating
from
imbalance