Proceedings of the National Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
122(12)
Published: March 20, 2025
Opioids
trigger
structural
and
functional
neural
adaptations
of
the
reward
circuit
that
lead
to
dependence.
Synaptic
cell
adhesion
molecules
(CAMs)
play
a
pivotal
role
in
organization
present
prime
candidates
for
orchestrating
remodeling
connections
response
drug
exposure.
However,
contribution
CAMs
opioid-induced
rewiring
has
not
been
explored.
Here,
we
used
unbiased
molecular
profiling
identify
nucleus
accumbens
(NAc)
modulated
by
morphine
administration.
We
found
opioid
exposure
induces
expression
ELFN1,
CAM
selectively
expressed
cholinergic
interneurons
NAc.
determined
ELFN1
acts
trans-synaptically
modulate
strength
plasticity
glutamatergic
inputs
onto
neurons
via
recruitment
presynaptic
metabotropic
glutamate
receptor
4
(mGlu4).
Disruption
Elfn1
diminished
intake
self-administering
mice.
Together,
our
findings
key
factor
responsible
adjusting
effects
modulating
configuration
striatal
circuitry
an
experience-dependent
fashion
unveil
potential
therapeutic
target
combating
abuse.
Pharmacological Reviews,
Journal Year:
2022,
Volume and Issue:
74(1), P. 271 - 310
Published: Jan. 1, 2022
Neuronal
nicotinic
acetylcholine
receptors
(nAChRs)
regulate
the
rewarding
actions
of
nicotine
contained
in
tobacco
that
establish
and
maintain
smoking
habit.
nAChRs
also
aversive
properties
nicotine,
sensitivity
to
which
decreases
use
protects
against
disorder.
These
opposing
behavioral
reflect
nAChR
expression
brain
reward
aversion
circuits.
containing
α4
β2
subunits
are
responsible
for
high-affinity
binding
sites
densely
expressed
by
reward-relevant
neurons,
most
notably
dopaminergic,
GABAergic,
glutamatergic
neurons
ventral
tegmental
area.
High-affinity
can
incorporate
additional
subunits,
including
β3,
α6,
or
α5
with
resulting
subtypes
playing
discrete
dissociable
roles
stimulatory
on
dopamine
transmission.
circuits
participate
reactions
negative
affective
state
experienced
during
withdrawal.
α3
β4
low-affinity
enriched
involved
aversion,
medial
habenula,
interpeduncular
nucleus,
nucleus
solitary
tract,
expressed.
aversion-related
avoidance
behaviors,
genetic
variation
modifies
function
these
increases
vulnerability
dependence
smoking-related
diseases.
Here,
we
review
molecular,
cellular,
circuit-level
mechanisms
through
elicits
adaptations
processes
drive
development
dependence.
Significance
Statement
Tobacco
disorder
form
habitual
cigarette
regular
other
tobacco-related
products
is
a
major
cause
death
disease
worldwide.
This
article
reviews
contribute
Journal of Neurorestoratology,
Journal Year:
2022,
Volume and Issue:
10(2), P. 100002 - 100002
Published: June 1, 2022
Acetylcholine
(ACh)
is
one
of
the
most
important
neurotransmitters
in
central
cholinergic
system;
it
specifically
binds
to
muscarinic
and
nicotinic
receptors
degraded
by
acetylcholinesterase
(AChE).
ACh
plays
a
crucial
role
learning
memory.
It
generally
believed
that,
nervous
system,
promotes
conduction
brain
nerves
accelerates
information
transmission.
Besides,
increasing
levels
can
enhance
memory
ability
comprehensively
improve
function.
Thus,
AChE
inhibitors
(AChEI),
which
inhibit
degradation
AChE,
have
been
used
treat
Alzheimer's
disease
(AD)
Parkinson's
dementia
(PDD).
However,
recent
studies
shown
that
excessive
system
impairs
Here
we
review
roles
memory;
focus
on
adverse
effects
ACh,
possible
mechanisms,
bidirectional
pathology
cure
AD
PDD.
We
conclude
timing
dose
administration
should
be
carefully
prescreened
when
using
alleviate
patients.
Trends in Pharmacological Sciences,
Journal Year:
2022,
Volume and Issue:
43(12), P. 1098 - 1112
Published: Oct. 20, 2022
Modern
interest
in
muscarinic
acetylcholine
receptor
(mAChR)
activators
for
schizophrenia
began
the
1990s
when
xanomeline,
an
M1/M4-preferring
mAChR
agonist
developed
cognitive
symptoms
of
Alzheimer's
disease
(AD),
had
unexpected
antipsychotic
activity.
However,
strategies
to
address
tolerability
concerns
associated
with
activation
peripheral
mAChRs
were
not
available
at
that
time.
The
discovery
specific
targeted
ligands
and
combination
treatments
reduce
engagement
have
advanced
potential
as
effective
psychotic
disorders.
This
review
provides
perspectives
on
background
identification
antipsychotics,
advances
preclinical
understanding
targets,
current
state
under
active
clinical
development
schizophrenia.
ACS Chemical Neuroscience,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 11, 2025
Voluntary
movement,
motivation,
and
reinforcement
learning
depend
on
the
activity
of
ventral
midbrain
neurons,
which
extend
axons
to
release
dopamine
(DA)
in
striatum.
These
neurons
exhibit
two
patterns
action
potential
activity:
low-frequency
tonic
that
is
intrinsically
generated
superimposed
high-frequency
phasic
bursts
are
driven
by
synaptic
inputs.
Ex
vivo
acute
striatal
brain
preparations
widely
employed
study
regulation
evoked
DA
but
very
different
kinetics
than
recordings.
To
investigate
relationship
between
neuronal
activity,
we
stimulated
slice
intended
mimic
were
interrupted
a
series
burst
stimuli.
Conditioning
with
altered
triggered
produced
kinetic
parameters
resemble
those
vivo.
In
absence
applied
nicotinic
acetylcholine
receptor
D2
antagonists
had
no
significant
effect
neurotransmitter
release,
repeated
slice.
contrast,
tonically
slices,
blockade
decreased
amount
released
during
single-burst
facilitated
subsequent
bursts.
This
experimental
system
provides
means
reconcile
difference
ex
novel
approach
more
accurately
emulate
pre-
postsynaptic
mechanisms
control
axonal
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: April 8, 2020
Abstract
Assimilation
of
novel
strategies
into
a
consolidated
action
repertoire
is
crucial
function
for
behavioral
adaptation
and
cognitive
flexibility.
Acetylcholine
in
the
striatum
plays
pivotal
role
such
adaptation,
its
release
has
been
causally
associated
with
activity
cholinergic
interneurons.
Here
we
show
that
midbrain,
previously
unknown
source
acetylcholine
striatum,
major
contributor
to
transmission
striatal
complex.
Neurons
pedunculopontine
laterodorsal
tegmental
nuclei
synapse
interneurons
give
rise
excitatory
responses.
Furthermore,
they
produce
uniform
inhibition
spiny
projection
neurons.
Inhibition
from
midbrain
terminals
impairs
association
contingencies
formation
habits
an
instrumental
task,
mimics
effects
observed
following
These
results
suggest
existence
two
hierarchically-organized
modes
where
are
modulated
by
neurons
midbrain.
Nature Communications,
Journal Year:
2020,
Volume and Issue:
11(1)
Published: Oct. 9, 2020
Striatal
activity
is
dynamically
modulated
by
acetylcholine
and
dopamine,
both
of
which
are
essential
for
basal
ganglia
function.
Synchronized
pauses
in
the
striatal
cholinergic
interneurons
(ChINs)
correlated
with
elevated
midbrain
dopaminergic
neurons,
whereas
synchronous
firing
ChINs
induces
local
release
dopamine.
The
mechanisms
underlying
ChIN
synchronization
its
interplay
dopamine
not
fully
understood.
Here
we
show
that
polysynaptic
inhibition
between
a
robust
network
motif
instrumental
shaping
ChINs.
Action
potentials
evoke
large
inhibitory
responses
multiple
neighboring
ChINs,
strong
enough
to
suppress
their
tonic
activity.
Using
combination
optogenetics
chemogenetics
involvement
tyrosine
hydroxylase-expressing
mediating
this
inhibition.
Inhibition
attenuated
afferents
acting
presynaptically
on
D2
receptors.
Our
results
present
novel
form
interaction
dynamics.
European Journal of Neuroscience,
Journal Year:
2021,
Volume and Issue:
53(8), P. 2421 - 2442
Published: Feb. 5, 2021
Abstract
The
critical
role
of
acetylcholine
(ACh)
in
the
basal
ganglia
is
evident
from
effect
cholinergic
agents
patients
suffering
several
related
neurological
disorders,
such
as
Parkinson's
disease,
Tourette
syndrome,
or
dystonia.
striatum
possesses
highest
density
ACh
markers
underlying
importance
this
structure.
Striatal
interneurons
(CINs)
are
responsible
for
bulk
striatal
ACh,
although
extrinsic
afferents
brainstem
structures
may
also
play
a
role.
CINs
tonically
active,
and
synchronized
pause
their
activity
occurs
following
presentation
salient
stimuli
during
behavioral
conditioning.
However,
synaptic
mechanisms
involved
not
fully
understood
physiological
response.
modulates
circuits
by
acting
on
muscarinic
nicotinic
receptors
existing
combinations
both
presynaptically
postsynaptically.
While
effects
through
have
received
particular
attention,
function
has
been
less
studied.
Here,
after
briefly
reviewing
relevant
results
regarding
expression
function,
I
will
focus
receptor
expressed
glutamatergic
dopaminergic
postsynaptically
diverse
populations.
review
recent
evidence
suggesting
involvement
different
GABAergic
sources
two
distinct
nicotinic‐receptor‐mediated
circuits:
disynaptic
inhibition
projection
neurons
recurrent
among
CINs.
A
better
understanding
help
to
develop
targeted
pharmacological
interventions
treat
brain
disorders
dystonia,
nicotine
addiction.
