bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Sept. 16, 2022
ABSTRACT
BACKGROUND
Post-traumatic
stress
disorder
(PTSD)
and
co-morbid
depression
are
frequently
associated
with
severe
symptoms,
poor
response
to
treatment
worse
prognosis.
Due
the
absence
of
a
suitable
animal
model,
little
is
known
about
biological
basis
comorbidity,
severely
limiting
discovery
new
more
effective
options.
The
Flinders
Sensitive
Line
rats
(FSL)
well-validated,
selectively
bred
model
depression.
However,
several
its
features,
such
as
cognitive
deficits
altered
hypothalamic-pituitary-adrenal
(HPA)
axis
response,
also
match
symptomatic
clusters
PTSD.
In
parallel,
resistant
counterpart,
Resistant
(FRL),
extensively
used
simple
control.
Still,
performance
compared
original
strain,
Sprague
Dawley
(SD),
from
which
FSL/FRL
was
originally
derived.
AIMS
Characterizing
behavioural
mechanisms
involved
in
FSL,
FRL
SD
fear-memory
paradigms.
METHODS
animals
were
submitted
tests
assessing
hippocampal-dependent
fear-related
memory.
Subsequently,
plasticity
factors
endocrine
responses
analysed
elucidate
molecular
for
observed
alterations.
RESULTS
We
found
that
presented
intact
recognition
memory
innate
fear
but
could
not
properly
display
conditioned
Conditioned
Fear
Conditioning
(CFC)
paradigm.
FSL
animals,
despite
Novel
Object
Recognition
task
(NOR),
showed
similar
levels
SD,
impairments
extinction
learning,
feature
highly
related
alterations
accompanied
by
plasma
corticosterone
hippocampal
expression
glucocorticoid
receptor
FKBP51.
CONCLUSION
For
first
time,
we
demonstrate
an
resilience
vulnerability
PTSD
results
suggest
endophenotypes
may
be
based
on
aberrant
hippocampus.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: July 5, 2022
Abstract
One
of
the
neuropathological
hallmarks
Alzheimer’s
disease
(AD)
is
accumulation
amyloid-β
(Aβ)
plaques,
which
preceded
by
intraneuronal
build-up
toxic,
aggregated
Aβ
during
progression.
plaques
are
first
deposited
in
neocortex
before
appearing
medial
temporal
lobe,
and
tau
pathology
with
subsequent
neurodegeneration
latter
anatomical
region
causes
early
memory
impairments
patients.
Current
research
suggests
that
may
begin
superficial
layers
lateral
entorhinal
cortex
(LEC).
To
examine
whether
manipulation
neuronal
activity
LEC
layer
II
neurons
affected
levels
downstream
perforant
path
terminals
hippocampus
(HPC),
we
used
a
chemogenetic
approach
to
selectively
chronically
silence
young
aged
3xTg
AD
mice
monitored
its
effect
on
HPC.
Chronic
silencing
led
reduced
projection
HPC,
compared
controls.
Early
HPC
correlated
LEC,
subiculum
being
earliest
subregion
involved,
our
findings
give
evidence
neuropathology
originating
select
populations.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 1, 2024
ABSTRACT
The
rodent
hippocampus
is
a
spatially
organized
neuronal
network
that
supports
the
formation
of
spatial
and
episodic
memories.
We
conducted
bulk
RNA
sequencing
transcriptomics
experiments
to
measure
gene
expression
changes
in
dorsal
following
recall
active
place
avoidance
(APA)
memory.
Through
sequencing,
we
examined
memory
across
functionally
distinct
subregions
hippocampus.
found
induced
differentially
expressed
genes
(DEGs)
CA1
CA3
hippocampal
were
enriched
with
involved
synaptic
transmission
plasticity,
while
DEGs
dentate
gyrus
(DG)
energy
balance
ribosomal
function.
transcriptomics,
an
array
spots
encompassing
putative
memory-associated
ensembles
marked
by
IEGs
Arc
,
Egr1
c-Jun
.
Within
samples
from
both
trained
untrained
mice,
subpopulations
transcriptomic
these
transcriptomically
one
another.
detected
between
+
-spots
exclusively
mouse
several
memory-related
ontology
terms,
including
“regulation
plasticity”
“memory.”
Our
results
suggest
APA
supported
regionalized
profiles
separating
DG,
transcriptionally
IEG
expressing
spots,
biological
processes
related
plasticity
as
defining
difference
-spatial
spots.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: June 7, 2024
Abstract
Parvalbumin
(PV)-expressing
GABAergic
neurons
of
the
basal
forebrain
(BFPVNs)
were
proposed
to
serve
as
a
rapid
and
transient
arousal
system,
yet
their
exact
role
in
awake
behaviors
remains
unclear.
We
performed
bulk
calcium
measurements
electrophysiology
with
optogenetic
tagging
from
horizontal
limb
diagonal
band
Broca
(HDB)
while
male
mice
performing
an
associative
learning
task.
BFPVNs
responded
distinctive,
phasic
activation
punishment,
but
showed
slower
delayed
responses
reward
outcome-predicting
stimuli.
Optogenetic
inhibition
during
punishment
impaired
formation
cue-outcome
associations,
suggesting
causal
learning.
received
strong
inputs
hypothalamus,
septal
complex
median
raphe
region,
they
synapsed
on
diverse
cell
types
key
limbic
structures,
where
broadcasted
information
about
aversive
propose
that
arousing
effect
is
recruited
by
stimuli
crucial
functions.
Brain Communications,
Journal Year:
2024,
Volume and Issue:
6(5)
Published: Jan. 1, 2024
Abstract
Addiction
to
psychoactive
substances
is
a
maladaptive
learned
behaviour.
Contexts
surrounding
drug
use
integrate
this
aberrant
mnemonic
process
and
hold
strong
relapse-triggering
ability.
Here,
we
asked
where
context
salience
might
be
concurrently
represented
in
the
brain
during
retrieval
of
drug–context
paired
associations.
For
this,
developed
morphine-conditioned
place
preference
protocol
that
allows
contextual
stimuli
presentation
inside
magnetic
resonance
imaging
scanner
investigated
differences
activity
connectivity
at
recall.
We
found
context-specific
responses
stimulus
onset
multiple
regions,
namely,
limbic,
sensory
striatal.
Differences
functional
interconnectivity
were
among
amygdala,
lateral
habenula,
septum.
also
alterations
resting-state
increased
centrality
septum
proposed
limbic
network,
as
well
habenula
hippocampal
‘cornu
ammonis’
1
region,
after
associative
drug–context.
Finally,
pre-
conditioned
amygdala
was
predictive
inter-individual
score
differences.
Overall,
our
findings
show
saline-paired
contexts
establish
distinct
memory
traces
overlapping
microcircuits
intrinsic
septum,
likely
underlies
individual
learning
opioid
exposure.
have
identified
maps
acquisition
drug-related
may
support
ability
opioid-associated
cues.
These
clarify
sensitivity
vulnerability
seen
addiction
opioids
humans.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 19, 2024
Background:
In
rodents,
third-trimester
equivalent
alcohol
exposure
(TTAE)
produces
significant
deficits
in
hippocampal-dependent
memory
processes
such
as
contextual
fear
conditioning
(CFC).
The
present
study
sought
to
characterize
changes
both
behavior
and
Fos+
neurons
following
CFC
ethanol
(EtOH)-treated
versus
saline-treated
mice
using
TRAP2:Ai14
that
permanently
label
a
tamoxifen
injection.
We
hypothesized
TTAE
would
produce
long-lasting
disruptions
the
networks
engaged
with
particular
emphasis
on
limbic
system.
Methods:
On
postnatal
day
7,
received
either
two
injections
of
saline
or
2.5
g/kg
EtOH
spaced
2
hours
apart.
were
left
undisturbed
until
they
reached
adulthood,
at
which
point
underwent
CFC.
After
context
2,
Brain
tissue
was
harvested.
Slides
automatically
imaged
Zeiss
AxioScanner.
Manual
counts
priori
regions
interest
conducted.
Automated
performed
whole
brain
QUINT
2D
stitching
pipeline.
Last,
novel
network
analyses
applied
identify
future
interest.
Results:
reduced
recall
neural
density
increased
CA1
CA3.
anteroventral
(AV)
anterodorsal
thalamus.
system
showed
hyperconnectivity
male
AV
shifted
affinity
towards
hippocampal
subregions.
subparafascicular
area
basomedial
amygdalar
nucleus
implicated
important
mediators.
Discussion:
These
results
suggest
is
mediated
by
disrupted
TTAE.
Given
increase
CA3
activity,
potential
hypothesis
causes
encoding
1
conditioning.
Future
studies
will
aim
determine
whether
this
disruption
specifically
affects
retrieval
memories.
Frontiers in Molecular Neuroscience,
Journal Year:
2024,
Volume and Issue:
17
Published: Oct. 31, 2024
The
rodent
hippocampus
is
a
spatially
organized
neuronal
network
that
supports
the
formation
of
spatial
and
episodic
memories.
We
conducted
bulk
RNA
sequencing
transcriptomics
experiments
to
measure
gene
expression
changes
in
dorsal
following
recall
active
place
avoidance
(APA)
memory.
Through
sequencing,
we
examined
memory
across
functionally
distinct
subregions
hippocampus.
found
induced
differentially
expressed
genes
(DEGs)
CA1
CA3
hippocampal
were
enriched
with
involved
synaptic
transmission
plasticity,
while
DEGs
dentate
gyrus
(DG)
energy
balance
ribosomal
function.
transcriptomics,
an
array
spots
encompassing
putative
memory-associated
ensembles
marked
by
IEGs
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 8, 2024
Abstract
Although
many
methods
for
automated
fluorescent-labeled
cell
detection
have
been
proposed,
not
all
of
them
assume
a
highly
inhomogeneous
background
arising
from
complex
biological
structures.
Here,
we
propose
an
algorithm
that
accounts
and
subtracts
the
by
avoiding
high-intensity
pixels
in
blur
filtering
calculation.
Cells
were
detected
intensity
thresholding
background-subtracted
image,
algorithm’s
performance
was
tested
on
NeuN-
c-Fos-stained
images
mouse
prefrontal
cortex
hippocampal
dentate
gyrus.
In
addition,
applications
c-Fos
positive
counting
quantification
expression
level
double-labeled
cells
demonstrated.
Our
method
after
assumption
(ADABA)
offers
advantage
high-throughput
unbiased
analysis
regions
with
structures
produce
background.
Highlights
-
We
proposed
to
subtract
pattern.
(79/85)
automatically
image.
(71/85)
The
results
corresponded
manual
detection.
(73/85)
Detection
IEG
overlapping
neural
marker
(85/85)