bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 27, 2024
ABSTRACT
Contextual
fear
conditioning
is
a
classical
laboratory
task
that
tests
associative
memory
formation
and
recall.
Techniques
such
as
multi-photon
microscopy
holographic
stimulation
offer
tremendous
opportunities
to
understand
the
neural
underpinnings
of
these
memories.
However,
techniques
generally
require
animals
be
head-fixed.
There
are
few
paradigms
test
contextual
in
head-fixed
mice,
none
where
behavioral
outcome
following
freezing,
most
common
measure
freely
moving
animals.
To
address
this
gap,
we
developed
paradigm
mice
using
virtual
reality
(VR)
environments.
We
designed
an
apparatus
deliver
tail
shocks
(unconditioned
stimulus,
US)
while
navigated
VR
environment
(conditioned
CS).
The
acquisition
was
tested
when
were
reintroduced
shock-paired
day.
three
different
variations
and,
all
them,
observed
increased
conditioned
response
characterized
by
freezing
behavior.
This
especially
prominent
during
first
trial
environment,
compared
neutral
received
no
shocks.
Our
results
demonstrate
can
VR,
discriminate
between
feared
context,
display
response,
similar
behaving
Furthermore,
two-photon
microscope,
imaged
from
large
populations
hippocampal
CA1
neurons
before,
during,
conditioning.
findings
reconfirmed
those
literature
on
animals,
showing
place
cells
undergo
remapping
show
narrower
fields
approach
offers
new
study
mechanisms
underlying
formation,
recall,
extinction
As
preparation
compatible
with
stimulation,
it
enables
long-term
tracking
manipulation
throughout
distinct
stages
provides
subcellular
resolution
for
investigating
axonal,
dendritic,
synaptic
dynamics
real-time.
Neuropsychopharmacology,
Journal Year:
2024,
Volume and Issue:
49(13), P. 1951 - 1957
Published: Aug. 13, 2024
The
infralimbic
(IL)
division
of
the
medial
prefrontal
cortex
(mPFC)
is
a
crucial
site
for
extinction
conditioned
fear
memories
in
rodents.
Recent
work
suggests
that
neuronal
plasticity
IL
occurs
during
(or
soon
after)
conditioning
enables
subsequent
IL-dependent
learning.
We
therefore
hypothesized
pharmacological
activation
after
would
promote
fear.
To
test
this
hypothesis,
we
characterized
effects
post-conditioning
infusions
GABA
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 31, 2024
Abstract
The
ability
to
extinguish
contextual
fear
in
a
changing
environment
is
crucial
for
animal
survival.
Recent
data
support
the
role
of
thalamic
nucleus
reuniens
(RE)
and
its
projections
dorsal
hippocampal
CA1
area
(RE→dCA1)
this
process.
However,
it
remains
poorly
understood
how
RE
impacts
dCA1
neurons
during
extinction
(CFE).
Here,
we
reveal
that
RE→dCA1
pathway
contributes
by
affecting
CFE-induced
molecular
remodeling
excitatory
synapses.
Anatomical
tracing
chemogenetic
manipulation
mice
demonstrate
form
synapses
regulate
synaptic
transmission
stratum
oriens
(SO)
lacunosum-moleculare
(SLM)
area,
but
not
radiatum
(SR).
We
also
observe
CFE-specific
structural
changes
expression
scaffold
protein,
PSD-95,
both
strata
innervated
RE,
SR.
Interestingly,
only
SLM
are
specific
dendrites
RE.
To
further
projection
CFE,
brief
inhibition
CFE
session
persistently
impairs
formation
memory
PSD-95
levels
SLM.
Thus,
our
indicate
participates
regulating
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: March 27, 2024
The
infralimbic
(IL)
division
of
the
medial
prefrontal
cortex
(mPFC)
is
a
crucial
site
for
extinction
conditioned
fear
memories
in
rodents.
Recent
work
suggests
that
neuronal
plasticity
IL
occurs
during
(or
soon
after)
conditioning
enables
subsequent
IL-dependent
learning.
We
therefore
hypothesized
pharmacological
activation
after
would
promote
fear.
To
test
this
hypothesis,
we
characterized
effects
post-conditioning
infusions
GABA
Communications Biology,
Journal Year:
2024,
Volume and Issue:
7(1)
Published: June 14, 2024
Abstract
Benzodiazepines,
commonly
used
for
anxiolytics,
hinder
conditioned
fear
extinction,
and
the
underlying
circuit
mechanisms
are
unclear.
Utilizing
remimazolam,
an
ultra-short-acting
benzodiazepine,
here
we
reveal
its
impact
on
thalamic
nucleus
reuniens
(RE)
interconnected
hippocamposeptal
circuits
during
extinction.
Systemic
or
RE-specific
administration
of
remimazolam
impedes
extinction
by
reducing
RE
activation
through
A
type
GABA
receptors.
Remimazolam
enhances
long-range
GABAergic
inhibition
from
lateral
septum
(LS)
to
RE,
compromised
projects
ventral
hippocampus
(vHPC),
which
in
turn
sends
projections
characterized
feed-forward
neurons
LS.
This
is
coupled
with
LS
collectively
constituting
overall
positive
feedback
construct
that
promotes
negates
facilitation
disrupting
this
circuit.
Thus,
disrupts
caused
intermediation,
offering
mechanistic
insights
dilemma
combining
anxiolytics
extinction-based
exposure
therapy.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: May 7, 2024
Abstract
Benzodiazepines,
commonly
used
for
anxiolytics,
hinder
conditioned
fear
extinction,
and
the
underlying
circuit
mechanisms
are
unclear.
Utilizing
remimazolam,
an
ultra-short-acting
benzodiazepine,
we
reveal
its
impact
on
thalamic
nucleus
reuniens
(RE)
interconnected
hippocamposeptal
circuits
during
extinction.
Systemic
or
RE-specific
administration
of
remimazolam
impedes
extinction
by
reducing
RE
activation
through
A
type
GABA
receptors.
Remimazolam
enhances
long-range
GABAergic
inhibition
from
lateral
septum
(LS)
to
RE,
compromised
projects
ventral
hippocampus
(vHPC),
which
in
turn
sends
projections
characterized
feed-forward
neurons
LS.
This
is
coupled
with
LS
collectively
constituting
overall
positive
feedback
construct
that
promotes
negates
facilitation
disrupting
this
circuit.
Thus,
disrupts
caused
intermediation,
offering
mechanistic
insights
dilemma
combining
anxiolytics
extinction-based
exposure
therapy.
