bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 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.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Окт. 24, 2023
Abstract
The
adaptive
regulation
of
fear
memories
is
a
crucial
neural
function
that
prevents
inappropriate
expression.
Fear
can
be
acquired
through
contextual
conditioning
(CFC)
which
relies
on
the
hippocampus.
thalamic
nucleus
reuniens
(NR)
necessary
to
extinguish
and
innervates
hippocampal
CA1.
However,
role
NR-CA1
pathway
in
unknown.
We
developed
head-restrained
virtual
reality
CFC
paradigm,
demonstrate
mice
acquire
context-dependent
responses.
found
inhibiting
following
lengthens
duration
fearful
freezing
epochs,
increases
generalization,
delays
extinction.
Using
vivo
imaging,
we
recorded
NR-axons
innervating
CA1
become
tuned
CFC.
conclude
actively
suppresses
by
disrupting
memory
retrieval
during
behavior,
process
also
reduces
generalization
accelerates
Frontiers in Behavioral Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Фев. 2, 2024
The
regulation
of
fear
memories
is
critical
for
adaptive
behaviors
and
dysregulation
these
processes
implicated
in
trauma-
stress-related
disorders.
Treatments
disorders
include
pharmacological
interventions
as
well
exposure-based
therapies,
which
rely
upon
extinction
learning.
Considerable
attention
has
been
directed
toward
elucidating
the
neural
mechanisms
underlying
In
this
review,
we
will
discuss
historic
discoveries
emerging
evidence
on
memories.
We
focus
circuits
regulating
acquisition
Pavlovian
conditioning
rodent
models,
particularly
role
medial
prefrontal
cortex
hippocampus
contextual
control
extinguished
also
consider
new
work
revealing
an
important
thalamic
nucleus
reuniens
modulation
prefrontal-hippocampal
interactions
learning
memory.
Finally,
explore
effects
stress
circuit
clinical
implications
findings.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 20, 2024
Summary
A
fundamental
question
in
neuroscience
is
how
memory
formation
shapes
brain
activity
at
the
level
of
populations
neurons.
Recent
studies
hippocampal
‘engram’
cells,
identified
by
immediate-early
genes
(IEGs)
induced
learning,
propose
that
these
act
as
a
neuronal
substrate
for
storage.
The
current
framework
engram
proposes
cells
join
ensembles
based
on
increased
intrinsic
excitability,
and
after
initial
they
co-activate
to
support
retrieval.
However,
direct
evidence
population
dynamics
evolve
across
learning
limited.
Here
we
combined
activity-dependent
genetic
tagging
two-photon
calcium
imaging
characterize
CA1
before
learning.
We
observed
spontaneous
two
days
predicted
tagging,
consistent
with
model
which
fluctuations
bias
into
forming
assemblies.
Surprisingly,
were
unable
detect
rates
or
pairwise
correlations
amongst
tagged
neurons
These
results
computational
network
models
incorporate
strong
specific
inhibitory
connections,
supporting
idea
excitatory/inhibitory
balance
may
play
key
role
dynamics.
Together
highlight
potential
slow
time
scale
excitability
driving
suggest
excitatory-inhibitory
regulate
cell
co-activation.
Highlights
Tracked
Fos
Spontaneous
predicts
TetTagging.
No
changes
TetTagged
Modeling
suggests
E/I
regulates
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 20, 2024
Abstract
Aversive
experiences
lead
to
the
formation
of
long-lasting
memories.
Despite
need
better
understand
how
enduring
fear
memories
can
be
attenuated,
underlying
brain
circuits
remain
largely
unknown.
In
this
study,
employing
a
combination
genetic
manipulations,
neuronal
circuit
mapping,
and
chemogenetics
in
mice,
we
identify
new
projection
from
thalamic
nucleus
reuniens
(RE)
medial
septum
(MS),
show
that
is
involved
extinction
remote
(30-day
old),
but
not
recent
(1-day
These
findings
provide
first
functional
description
RE→MS
highlight
significance
thalamo-septal
regions
memory
organization
as
function
age,
phenomenon
known
systems
consolidation.
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
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.
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.
JHEP Reports,
Год журнала:
2023,
Номер
6(3), С. 100992 - 100992
Опубликована: Дек. 21, 2023
Cognitive
dysfunction
is
an
increasingly
recognised
manifestation
of
metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD),
but
the
mechanistic
link
remains
unclear.
The
aim
this
study
was
to
investigate
hypothesis
that
experimental
MASLD
leads
cognitive
via
systemic
inflammation
and
neuroinflammation.
Neuroscience & Biobehavioral Reviews,
Год журнала:
2024,
Номер
163, С. 105762 - 105762
Опубликована: Июнь 12, 2024
The
reuniens
(Re)
nucleus
is
located
in
the
ventral
midline
thalamus.
It
has
fostered
increasing
interest,
not
only
for
its
participation
a
variety
of
cognitive
functions
(e.g.,
spatial
working
memory,
systemic
consolidation,
reconsolidation,
extinction
fear
or
generalization),
but
also
neuroanatomical
positioning
as
bidirectional
relay
between
prefrontal
cortex
(PFC)
and
hippocampus
(HIP).
In
this
review
we
compile
discuss
recent
studies
having
tackled
possible
implication
Re
behavioral
flexibility,
major
PFC-dependent
executive
function
controlling
goal-directed
behaviors.
Experiments
considered
explored
role
perseveration,
reversal
learning,
extinction,
set-shifting.
They
point
to
contribution
mainly
by
connections
with
PFC,
possibly
those
hippocampus,
even
amygdala,
at
least
fear-related
behavior.
As
such,
could
be
crucial
crossroad
supporting
PFC-orchestrated
ability
cope
new,
potentially
unpredictable
environmental
contingencies,
thus
flexibility
adaption.