Cell Reports,
Journal Year:
2023,
Volume and Issue:
42(9), P. 113066 - 113066
Published: Aug. 31, 2023
Fear-related
disorders
arise
from
inefficient
fear
extinction
and
have
immeasurable
social
economic
costs.
Here,
we
characterize
mouse
phenotypes
that
spontaneously
show
fear-independent
behavioral
traits
predicting
adaptive
or
maladaptive
extinction.
We
find
that,
already
before
conditioning,
specific
morphological,
electrophysiological,
transcriptomic
patterns
of
cortical
amygdala
pyramidal
neurons
predispose
to
fear-related
disorders.
Finally,
by
using
an
optogenetic
approach,
the
possibility
rescue
activating
infralimbic
impair
prelimbic
neurons.
Nature,
Journal Year:
2024,
Volume and Issue:
627(8003), P. 374 - 381
Published: Feb. 7, 2024
Abstract
Memory
encodes
past
experiences,
thereby
enabling
future
plans.
The
basolateral
amygdala
is
a
centre
of
salience
networks
that
underlie
emotional
experiences
and
thus
has
key
role
in
long-term
fear
memory
formation
1
.
Here
we
used
spatial
single-cell
transcriptomics
to
illuminate
the
cellular
molecular
architecture
memory.
We
identified
transcriptional
signatures
subpopulations
neurons
astrocytes
were
memory-specific
persisted
for
weeks.
These
implicate
neuropeptide
BDNF
signalling,
MAPK
CREB
activation,
ubiquitination
pathways,
synaptic
connectivity
as
components
Notably,
upon
formation,
neuronal
subpopulation
defined
by
increased
Penk
decreased
Tac
expression
constituted
most
prominent
component
engram
amygdala.
changes
observed
both
with
RNA
sequencing
single-molecule
intact
slices,
providing
rich
map
engram.
data
enabled
us
determine
this
interacts
adjacent
astrocytes,
functional
experiments
show
require
interactions
encode
Neuron,
Journal Year:
2024,
Volume and Issue:
112(14), P. 2289 - 2303
Published: May 9, 2024
The
property
of
mixed
selectivity
has
been
discussed
at
a
computational
level
and
offers
strategy
to
maximize
power
by
adding
versatility
the
functional
role
each
neuron.
Here,
we
offer
biologically
grounded
implementational-level
mechanistic
explanation
for
in
neural
circuits.
We
define
pure,
linear,
nonlinear
discuss
how
these
response
properties
can
be
obtained
simple
Neurons
that
respond
multiple,
statistically
independent
variables
display
selectivity.
If
their
activity
expressed
as
weighted
sum,
then
they
exhibit
linear
selectivity;
otherwise,
Neural
representations
based
on
diverse
are
high
dimensional;
hence,
confer
enormous
flexibility
downstream
readout
circuit.
However,
circuit
cannot
possibly
encode
all
possible
mixtures
simultaneously,
this
would
require
combinatorially
large
number
neurons.
Gating
mechanisms
like
oscillations
neuromodulation
solve
problem
dynamically
selecting
which
transmitted
readout.
Annals of the New York Academy of Sciences,
Journal Year:
2023,
Volume and Issue:
1525(1), P. 70 - 87
Published: May 2, 2023
Abstract
A
functional
interplay
of
bottom‐up
and
top‐down
processing
allows
an
individual
to
appropriately
respond
the
dynamic
environment
around
them.
These
modalities
can
be
represented
as
attractor
states
using
a
dynamical
systems
model
brain.
The
transition
probability
move
from
one
state
another
is
dependent
on
stability,
depth,
neuromodulatory
tone,
tonic
changes
in
plasticity.
However,
how
does
relationship
between
these
change
disease
states,
such
anxiety
or
depression?
We
describe
Marr's
computational‐algorithmic‐implementation
perspective
understand
depressive
anxious
states.
illustrate
examples
basolateral
amygdala
signaling
projections
medial
prefrontal
cortex
internal
projections.
Understanding
dynamics
help
us
better
multifaceted
elements
depression.
Neuron,
Journal Year:
2023,
Volume and Issue:
111(23), P. 3789 - 3801.e6
Published: Sept. 29, 2023
Relief,
the
appetitive
state
after
termination
of
aversive
stimuli,
is
evolutionarily
conserved.
Understanding
behavioral
role
this
well-conserved
phenomenon
and
its
underlying
neurobiological
mechanisms
are
open
important
questions.
Here,
we
discover
that
magnitude
relief
from
physical
stress
strongly
correlates
with
individual
resilience
to
depression-like
behaviors
in
chronic
stressed
mice.
Notably,
blocking
causes
vulnerability
behaviors,
whereas
natural
rewards
supplied
shortly
promotes
resilience.
Stress
mediated
by
reward-related
mesolimbic
dopamine
neurons,
which
show
minute-long,
persistent
activation
termination.
Circuitry-wise,
or
inhibition
circuits
downstream
ventral
tegmental
area
during
transient
period
bi-directionally
regulates
depression
These
results
reveal
an
evolutionary
function
identify
neural
substrate
mediating
effect.
Importantly,
our
data
suggest
a
strategy
augmenting
positive
valence
prevent
depression.
Cell Reports,
Journal Year:
2025,
Volume and Issue:
44(1), P. 115162 - 115162
Published: Jan. 1, 2025
Words
represent
a
uniquely
human
information
channel-humans
use
words
to
express
thoughts
and
feelings
assign
emotional
valence
experience.
Work
from
model
organisms
suggests
that
assignments
are
carried
out
in
part
by
the
neuromodulators
dopamine,
serotonin,
norepinephrine.
Here,
we
ask
whether
signaling
these
extends
word
semantics
humans
measuring
sub-second
neuromodulator
dynamics
thalamus
(N
=
13)
anterior
cingulate
cortex
6)
of
individuals
evaluating
positive,
negative,
neutrally
valenced
words.
Our
combined
results
suggest
modulate
release
both
cortex,
but
with
region-
valence-specific
response
patterns,
as
well
hemispheric
dependence
for
dopamine
cingulate.
Overall,
experiments
provide
evidence
neuromodulator-dependent
humans,
not
simple
one-valence-per-transmitter
fashion.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 7, 2025
Neuromodulatory
signaling
is
poised
to
serve
as
a
neural
mechanism
for
gain
control,
acting
crucial
tuning
factor
influence
neuronal
activity
by
dynamically
shaping
excitatory
and
inhibitory
fast
neurotransmission.
The
endocannabinoid
(eCB)
system,
the
most
widely
expressed
neuromodulatory
system
in
mammalian
brain,
known
filter
inputs
through
retrograde,
pre-synaptic
action.
However,
whether
eCBs
exert
retrograde
control
ultimately
facilitate
reward-seeking
behaviors
freely
moving
mammals
not
established.
Using
suite
of
vivo
physiological,
imaging,
genetic
machine
learning-based
approaches,
we
report
fundamental
role
controlling
behavioral
engagement
behavior
defined
thalamo-striatal
circuit.
Journal of Neurochemistry,
Journal Year:
2023,
Volume and Issue:
166(2), P. 189 - 200
Published: June 13, 2023
Abstract
The
neurotensin
system
spans
across
the
central
nervous
system,
to
enteric
(gut),
and
periphery
govern
behaviors
physiological
responses
that
tune
energy
balance
maintain
homeostasis.
Neurotensin
transmission
is
not
only
modulated
by
metabolic
signals,
itself
can
also
impact
state
exerting
control
over
consumption,
physical
activity,
satiety
signals.
Many
sensory
experiences
sleep
processes
are
dictated
neurotensinergic
activity
via
mechanisms
allow
organism
seeking
utilization
thrive
in
its
environment.
Given
broad
reach
signaling
has
homeostatic
landscape,
understanding
this
as
a
whole
examining
new
ways
target
for
therapeutic
efficacy
many
different
conditions
necessary.
image
Current Neuropharmacology,
Journal Year:
2023,
Volume and Issue:
22(5), P. 916 - 934
Published: Aug. 3, 2023
Neurotensin
(NT)
is
a
13-amino
acid
neuropeptide
widely
distributed
in
the
CNS
that
has
been
involved
pathophysiology
of
many
neural
and
psychiatric
disorders.
There
are
three
known
neurotensin
receptors
(NTSRs),
which
mediate
multiple
actions,
form
neurotensinergic
system
conjunction
with
NT.
NTSR1
main
mediator
NT,
displaying
effects
both
periphery,
while
NTSR2
mainly
expressed
brain
NTSR3
broader
expression
pattern.
In
this
review,
we
bring
together
up-to-date
studies
showing
an
involvement
different
aspects
stress
response
stress-related
disorders,
such
as
depression
anxiety,
post-traumatic
disorder
(PTSD)
its
associated
symptoms,
fear
memory
maternal
separation,
ethanol
addiction,
substance
abuse.
Emphasis
put
on
gene,
mRNA,
protein
alterations
NT
NTSRs,
well
behavioral
pharmacological
studies,
leading
to
evidence-based
suggestions
implicated
regulating
mechanisms
their
therapeutic
exploitation.
Stress
responses
anxiety
involve
NTSR1,
but
also
NTSR3.
primarily
depression,
secondarily
PTSD.
interrelated
drug
abuse
memory,
all
NTSRs
seem
be
consumption.
Some
actions
these
pathological
settings
may
driven
through
interactions
between
corticotrophin
releasing
factor
(CRF)
regulatory
contribution,
by
NT's
pro-inflammatory
mediating
actions.
