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.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 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
Controlling
action
and
thought
requires
the
capacity
to
stop
mental
processes.
Over
last
two
decades,
evidence
has
grown
that
a
domain-general
inhibitory
control
mechanism
supported
by
right
lateral
prefrontal
cortex
achieves
these
functions.
However,
current
views
of
neural
mechanisms
derive
largely
from
research
into
stopping
action.
Whereas
is
convenient
empirical
model,
it
does
not
invoke
inhibition
cannot
identify
its
unique
features.
Here
we
review
using
different
model
addresses
how
organisms
key
process
driving
thoughts:
memory
retrieval.
Retrieval
shares
anterior
dorsolateral
ventrolateral
with
stopping,
consistent
domain
general
mechanism;
however,
retrieval
also
recruits
distinct
fronto-temporal
pathway
determines
control’s
success.
For
example,
GABAergic
networks
within
hippocampus,
driven
polysynaptically
input
uniquely
contribute
suppression.
These
elements
raise
hypothesis
hippocampal
disinhibition
trans-diagnostic
factor
underlying
intrusive
thinking,
linking
proposed
preclinical
models
psychiatric
disorders
fear
extinction.
We
suggest
transdiagnostic
retrieval-stopping
deficits
underpin
broad
vulnerability
are
reflected
in
robust
aberrations
large-scale
brain
network
dynamics.
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Июнь 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.
Learning & Memory,
Год журнала:
2024,
Номер
31(9), С. a054022 - a054022
Опубликована: Сен. 1, 2024
G
protein-gated
inwardly
rectifying
K
+
(GIRK)
channels
mediate
the
postsynaptic
inhibitory
effect
of
many
neurotransmitters
in
hippocampus
and
are
implicated
neurological
disorders
characterized
by
cognitive
deficits.
Here,
we
show
that
enhancement
or
suppression
GIRK
channel
activity
dorsal
CA1
pyramidal
neurons
disrupted
novel
object
recognition
mice,
without
impacting
open
field
avoidance
behavior.
Contextual
fear
learning
was
also
unaffected,
but
extinction
contextual
male
mice.
Thus,
strength
regulates
select
task
performance
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 24, 2024
Abstract
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.
