Proceedings of the National Academy of Sciences,
Journal Year:
2025,
Volume and Issue:
122(18)
Published: April 28, 2025
The
extinction
of
conditioned
fear
responses
is
crucial
for
adaptive
behavior,
and
its
impairment
a
hallmark
anxiety
disorders
such
as
posttraumatic
stress
disorder.
Fear
takes
place
when
animals
form
new
memory
that
suppresses
the
original
memory.
In
case
context-dependent
memory,
formed
within
reward-responding
posterior
subset
basolateral
amygdala
(BLA)
genetically
marked
by
Ppp1r1b
+
neurons.
These
engram
cells
suppress
activity
fear-responding
Rspo2
present
in
anterior
BLA,
hence
extinction.
However,
neurological
nature
teaching
signal
instructs
formation
neurons
unknown.
Here,
we
demonstrate
ventral
tegmental
area
(VTA)
dopaminergic
signaling
drives
distinct
BLA
neuronal
populations.
We
show
populations
receive
topographically
divergent
inputs
from
VTA
via
differentially
expressed
dopamine
receptors.
Fiber
photometry
recordings
reveal
(DA)
time-locked
to
freezing
cessation
neurons,
but
not
Furthermore,
this
correlates
with
learning.
Finally,
using
projection-specific
optogenetic
manipulation,
find
activation
DA
projections
reward
accelerated
or
impaired
extinction,
respectively.
Together,
work
demonstrates
bidirectionally
controls
patterns
at
Physiological Reviews,
Journal Year:
2020,
Volume and Issue:
101(2), P. 611 - 681
Published: Sept. 24, 2020
This
article
reviews
the
behavioral
neuroscience
of
extinction,
phenomenon
in
which
a
behavior
that
has
been
acquired
through
Pavlovian
or
instrumental
(operant)
learning
decreases
strength
when
outcome
reinforced
it
is
removed.
Behavioral
research
indicates
neither
nor
operant
extinction
depends
substantially
on
erasure
original
but
instead
new
inhibitory
primarily
expressed
context
learned,
as
exemplified
by
renewal
effect.
Although
nature
inhibition
may
differ
and
either
case
decline
responding
depend
both
generalization
decrement
correction
prediction
error.
At
neural
level,
requires
tripartite
circuit
involving
amygdala,
prefrontal
cortex,
hippocampus.
Synaptic
plasticity
amygdala
essential
for
learning,
cortical
neurons
encoding
fear
memories
involved
retrieval.
Hippocampal-prefrontal
circuits
mediate
relapse
phenomena,
including
renewal.
Instrumental
involves
distinct
ensembles
corticostriatal,
striatopallidal,
striatohypothalamic
well
their
thalamic
returns
(extinction)
excitatory
(renewal
other
phenomena)
control
over
responding.
The
field
made
significant
progress
recent
decades,
although
fully
integrated
biobehavioral
understanding
still
awaits.
Cell,
Journal Year:
2018,
Volume and Issue:
175(3), P. 709 - 722.e15
Published: Sept. 20, 2018
Accurately
predicting
an
outcome
requires
that
animals
learn
supporting
and
conflicting
evidence
from
sequential
experience.
In
mammals
invertebrates,
learned
fear
responses
can
be
suppressed
by
experiencing
predictive
cues
without
punishment,
a
process
called
memory
extinction.
Here,
we
show
extinction
of
aversive
memories
in
Drosophila
specific
dopaminergic
neurons,
which
indicate
omission
punishment
is
remembered
as
positive
Functional
imaging
revealed
co-existence
intracellular
calcium
traces
different
places
the
mushroom
body
output
neuron
network
for
both
original
new
appetitive
memory.
Light
ultrastructural
anatomy
are
consistent
with
parallel
competing
being
combined
within
neurons
direct
avoidance.
Indeed,
extinction-evoked
plasticity
pair
these
neutralizes
potentiated
odor
response
imposed
learning.
Therefore,
flies
track
accuracy
expectations
accumulating
integrating
events.
Pharmacology & Therapeutics,
Journal Year:
2019,
Volume and Issue:
204, P. 107402 - 107402
Published: Aug. 27, 2019
Current
medication
for
anxiety
disorders
is
suboptimal
in
terms
of
efficiency
and
tolerability,
highlighting
the
need
improved
drug
treatments.
In
this
review
an
overview
drugs
being
studied
different
phases
clinical
trials
their
potential
treatment
fear-,
anxiety-
trauma-related
presented.
One
strategy
followed
development
refining
improving
compounds
interacting
with
existing
anxiolytic
targets,
such
as
serotonergic
prototypical
GABAergic
benzodiazepines.
A
more
innovative
approach
involves
search
novel
mechanisms
action
using
growing
knowledge
base
concerning
relevant
neurocircuitries
neurobiological
underlying
pathological
fear
anxiety.
The
target
systems
evaluated
include
glutamate,
endocannabinoid
neuropeptide
systems,
well
ion
channels
targets
derived
from
phytochemicals.
Examples
promising
candidates
currently
generalised
disorder,
social
panic
obsessive
compulsive
disorder
or
post-traumatic
stress
ketamine,
riluzole,
xenon
one
common
pharmacological
modulation
glutamatergic
neurotransmission,
neurosteroid
aloradine.
Finally,
D-cycloserine,
MDMA,
L-DOPA
cannabinoids
have
shown
efficacy
enhancing
fear-extinction
learning
humans.
They
are
thus
investigated
augmentative
speeding
up
long-term
effectiveness
exposure-based
psychotherapy,
which
could
render
chronic
dispensable
many
patients.
These
efforts
indicative
a
rekindled
interest
renewed
optimism
discovery
field,
after
decades
relative
stagnation.
Extinction
of
fear
responses
is
critical
for
adaptive
behavior
and
deficits
in
this
form
safety
learning
are
hallmark
anxiety
disorders.
However,
the
neuronal
mechanisms
that
initiate
extinction
largely
unknown.
Here
we
show,
using
single-unit
electrophysiology
cell-type
specific
fiber
photometry,
dopamine
neurons
ventral
tegmental
area
(VTA)
activated
by
omission
aversive
unconditioned
stimulus
(US)
during
extinction.
This
signal
occurred
specifically
beginning
when
US
unexpected,
correlated
strongly
with
learning.
Furthermore,
temporally-specific
optogenetic
inhibition
or
excitation
at
time
revealed
both
necessary
for,
sufficient
to
accelerate,
normal
These
results
identify
a
prediction
error-like
reveal
crucial
role
DA
