Biphasic Npas4 expression promotes inhibitory plasticity and suppression of fear memory consolidation in mice
Molecular Psychiatry,
Journal Year:
2024,
Volume and Issue:
29(7), P. 1929 - 1940
Published: Feb. 13, 2024
Long-term
memories
are
believed
to
be
encoded
by
unique
transcriptional
signatures
in
the
brain.
The
expression
of
immediate
early
genes
(IEG)
promotes
structural
and
molecular
changes
required
for
memory
consolidation.
Recent
evidence
has
shown
that
brain
is
equipped
with
mechanisms
not
only
promote,
but
actively
constrict
formation.
However,
it
remains
unknown
whether
IEG
may
play
a
role
suppression.
Here
we
uncovered
novel
function
neuronal
PAS
domain
protein
4
(Npas4),
as
an
inducible
suppressor
gene
highly
salient
aversive
experiences.
Using
contextual
fear
conditioning
paradigm,
found
low
stimulus
salience
leads
monophasic
Npas4
expression,
while
learning
induces
biphasic
hippocampus.
later
phase
requires
N-methyl-D-aspartate
(NMDA)
receptor
activity
independent
dopaminergic
neurotransmission.
Our
vivo
pharmacological
genetic
manipulation
experiments
suggested
restricts
consolidation
promote
behavioral
flexibility,
facilitating
extinction
specificity
responses.
Moreover,
immunofluorescence
electrophysiological
analysis
revealed
concomitant
increase
synaptic
input
from
cholecystokinin
(CCK)-expressing
interneurons.
results
demonstrate
how
experiences
evoke
temporal
patterns
fine-tune
our
study
provides
associated
suppression
possible
mechanism
balance
memories,
thereby
evade
formation
maladaptive
behavior.
Language: Английский
Cortico-subcortical networks that determine behavioral memory renewal are redefined by noradrenergic neuromodulation
Scientific Reports,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: March 20, 2025
Abstract
During
spatial
appetitive
extinction
learning
(EL),
rodents
learn
that
previously
rewarded
behavior
is
no
longer
rewarded.
Renewal
of
the
extinguished
enabled
by
re-exposure
to
context
in
which
occurred.
When
renewal
response
(RR)
unrewarded,
it
rapidly
followed
(RE).
Although
hippocampus
known
be
engaged,
whether
this
dynamic
supported
different
brain
networks
unclear.
To
clarify
this,
male
rats
engaged
context-dependent
memory
acquisition,
EL
and
RR
testing
a
T-Maze.
Fluorescence
situ
hybridization
disambiguated
somatic
immediate
early
gene
expression
neuronal
somata
or
RE.
Graph
analysis
revealed
pronounced
hippocampal
connectivity
with
retrosplenial
prefrontal
cortex
(PFC)
during
initial
RR.
By
contrast,
RE
was
accompanied
shift
towards
elevated
coordinated
activity
within
all
subfields.
Given
β-adrenergic
receptors
(β-AR)
regulate
memory,
we
activated
β-AR
further
scrutinize
these
network
effects.
This
enhanced
prevented
Effects
were
associated
initially
increased
thalamic-hippocampus
activity,
decrease
intraconnectivity
predominance
PFC.
Our
findings
highlight
critical
hippocampal-cortical-thalamic
underpins
behavior,
noradrenergic
neuromodulation
playing
pivotal
role
governing
circuit’s
dynamics.
Language: Английский
Dual-step pharmacological intervention for traumatic-like memories: implications from D-cycloserine and cannabidiol or clonidine in male and female rats
Psychopharmacology,
Journal Year:
2024,
Volume and Issue:
241(9), P. 1827 - 1840
Published: May 1, 2024
Language: Английский
Network-level changes in the brain underlie fear memory strength
eLife,
Journal Year:
2023,
Volume and Issue:
12
Published: June 27, 2023
The
strength
of
a
fear
memory
significantly
influences
whether
it
drives
adaptive
or
maladaptive
behavior
in
the
future.
Yet,
how
mild
and
strong
memories
differ
underlying
biology
is
not
well
understood.
We
hypothesized
that
this
distinction
may
be
exclusively
result
changes
within
specific
brain
regions,
but
rather
outcome
collective
connectivity
across
multiple
regions
neural
network.
To
test
this,
rats
were
conditioned
protocols
varying
intensities
to
generate
memories.
Neuronal
activation
driven
by
recall
was
measured
using
c-fos
immunohistochemistry
12
implicated
learning
memory.
interregional
coordinated
activity
computed
graph-based
functional
networks
generated
compare
at
systems
level.
Our
results
show
supported
well-connected
network
with
small-world
properties
which
amygdala
well-positioned
modulated
other
regions.
In
contrast,
disrupted
isolated
from
These
findings
indicate
differ,
implications
for
understanding
treating
disorders
dysregulation.
Language: Английский
Male rats emit aversive 44-kHz ultrasonic vocalizations during prolonged Pavlovian fear conditioning
eLife,
Journal Year:
2023,
Volume and Issue:
12
Published: June 23, 2023
Rats
are
believed
to
communicate
their
emotional
state
by
emitting
two
distinct
types
of
ultrasonic
vocalizations.
The
first
is
long
‘22-kHz’
vocalizations
(>300
ms,
<32-kHz)
with
constant
frequency,
signaling
aversive
states,
and
the
second
short
‘50-kHz’
calls
(<150
>32
kHz),
often
frequency-modulated,
in
appetitive
situations.
Here,
we
describe
emitted
at
a
higher
pitch
male
Wistar
spontaneously
hypertensive
rats
(SHR)
an
intensified
–
prolonged
fear
conditioning.
These
calls,
which
named
‘44-kHz’
vocalizations,
(>150
ms),
generally
frequency
(usually
within
35–50-kHz
range)
have
overall
spectrographic
image
similar
22-kHz
calls.
Some
44-kHz
comprised
both
22-kHz-like
44-kHz-like
elements.
Furthermore,
separate
clustering
methods
confirmed
that
these
can
be
separated
from
other
We
observed
associated
freezing
behavior
during
conditioning
training,
they
constituted
up
19.4%
all
most
them
appeared
next
each
forming
uniform
groups
(bouts).
also
show
some
rats’
responses
playback
were
more
akin
for
example,
heart
rate
changes,
whereas
intermediate
level
between
Our
results
suggest
wider
vocal
repertoire
than
previously
believed,
current
definitions
major
call
may
require
reevaluation.
hope
future
investigations
rat
models
human
diseases
will
contribute
expanding
our
understanding
therapeutic
strategies
related
psychiatric
conditions.
Language: Английский
Male rats emit aversive 44-kHz ultrasonic vocalizations during prolonged Pavlovian fear conditioning
eLife,
Journal Year:
2024,
Volume and Issue:
12
Published: Dec. 10, 2024
Rats
are
believed
to
communicate
their
emotional
state
by
emitting
two
distinct
types
of
ultrasonic
vocalizations.
The
first
is
long
‘22-kHz’
vocalizations
(>300
ms,
<32-kHz)
with
constant
frequency,
signaling
aversive
states,
and
the
second
short
‘50-kHz’
calls
(<150
>32
kHz),
often
frequency-modulated,
in
appetitive
situations.
Here,
we
describe
emitted
at
a
higher
pitch
male
Wistar
spontaneously
hypertensive
rats
(SHR)
an
intensified
–
prolonged
fear
conditioning.
These
calls,
which
named
‘44-kHz’
vocalizations,
(>150
ms),
generally
frequency
(usually
within
35–50-kHz
range)
have
overall
spectrographic
image
similar
22-kHz
calls.
Some
44-kHz
comprised
both
22-kHz-like
44-kHz-like
elements.
Furthermore,
separate
clustering
methods
confirmed
that
these
can
be
separated
from
other
We
observed
associated
freezing
behavior
during
conditioning
training,
they
constituted
up
19.4%
all
most
them
appeared
next
each
forming
uniform
groups
(bouts).
also
show
some
rats’
responses
playback
were
more
akin
for
example,
heart
rate
changes,
whereas
intermediate
level
between
Our
results
suggest
wider
vocal
repertoire
than
previously
believed,
current
definitions
major
call
may
require
reevaluation.
hope
future
investigations
rat
models
human
diseases
will
contribute
expanding
our
understanding
therapeutic
strategies
related
psychiatric
conditions.
Language: Английский