Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: July 17, 2024
Abstract
Adjusting
decision-making
under
uncertain
and
dynamic
situations
is
the
hallmark
of
intelligence.
It
requires
a
system
capable
converting
feedback
information
to
renew
internal
value.
The
anterior
cingulate
cortex
(ACC)
involves
in
error
reward
events
that
prompt
switching
or
maintenance
current
decision
strategies.
However,
it
unclear
whether
how
changes
stimulus-action
mapping
during
behavioral
adaptation
are
encoded,
nor
such
computation
drives
adaptation.
Here,
we
tracked
ACC
activity
male
mice
performing
go/no-go
auditory
discrimination
tasks
with
manipulated
stimulus-reward
contingencies.
Individual
neurons
integrate
outcome
value
representation
next-run
trials.
Dynamic
recruitment
them
determines
learning
rate
error-guided
iteration
adaptation,
forming
non-linear
feedback-driven
updating
secure
appropriate
switch.
Optogenetically
suppressing
significantly
slowed
down
without
interfering
execution
established
strategy.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Feb. 9, 2024
Abstract
Worldwide,
the
incidence
of
major
depressive
disorder
(MDD)
is
increasing
annually,
resulting
in
greater
economic
and
social
burdens.
Moreover,
pathological
mechanisms
MDD
underlying
effects
pharmacological
treatments
for
are
complex
unclear,
additional
diagnostic
therapeutic
strategies
still
needed.
The
currently
widely
accepted
theories
pathogenesis
include
neurotransmitter
receptor
hypothesis,
hypothalamic-pituitary-adrenal
(HPA)
axis
cytokine
neuroplasticity
hypothesis
systemic
influence
but
these
cannot
completely
explain
mechanism
MDD.
Even
it
hard
to
adopt
only
one
reveal
MDD,
thus
recent
years,
great
progress
has
been
made
elucidating
roles
multiple
organ
interactions
identifying
novel
approaches
multitarget
modulatory
strategies,
further
revealing
disease
features
Furthermore,
some
newly
discovered
potential
targets
studied
antidepressants
have
attracted
widespread
attention,
reagents
even
approved
clinical
treatment
methods
such
as
phototherapy
acupuncture
effective
improvement
symptoms.
In
this
work,
we
comprehensively
summarize
latest
research
on
diagnosis
preventive
medicines,
well
related
trials.
Fluctuations
in
brain
and
behavioral
state
are
supported
by
broadly
projecting
neuromodulatory
systems.
In
this
study,
we
use
mesoscale
two-photon
calcium
imaging
to
examine
spontaneous
activity
of
cholinergic
noradrenergic
axons
awake
mice
order
determine
the
interaction
between
arousal/movement
transitions
across
dorsal
cortex
at
distances
separated
up
4
mm.
We
confirm
that
GCaMP6s
within
axonal
projections
both
basal
forebrain
locus
coeruleus
neurons
track
arousal,
indexed
as
pupil
diameter,
changes
engagement,
reflected
bouts
whisker
movement
and/or
locomotion.
The
broad
coordination
even
distant
segments
indicates
these
systems
can
communicate,
part,
through
a
global
signal,
especially
relation
state.
addition
coordinated
activity,
also
find
evidence
subpopulation
may
exhibit
heterogeneity
appears
be
independent
our
measures
By
monitoring
interneurons
cortex,
found
cells
state-dependent
(arousal/movement)
activity.
These
results
demonstrate
provide
prominent
synchronized
signal
related
state,
therefore
contribute
cortical
excitability.
Prediction
errors
are
differences
between
expected
and
actual
sensory
input
thought
to
be
key
computational
signals
that
drive
learning
related
plasticity.
One
way
prediction
could
is
by
activating
neuromodulatory
systems
gate
The
catecholaminergic
locus
coeruleus
(LC)
a
major
system
involved
in
neuronal
plasticity
the
cortex.
Using
two-photon
calcium
imaging
mice
exploring
virtual
environment,
we
found
activity
of
LC
axons
cortex
correlated
with
magnitude
unsigned
visuomotor
errors.
response
profiles
were
similar
both
motor
visual
cortical
areas,
indicating
broadcast
throughout
dorsal
While
layer
2/3
primary
cortex,
optogenetic
stimulation
facilitated
stimulus-specific
suppression
responses
during
locomotion.
This
-
induced
minutes
recapitulated
effect
on
scale
normally
observed
development
across
days.
We
conclude
activity,
facilitates
sensorimotor
consistent
role
modulating
rates.
Neuroscience & Biobehavioral Reviews,
Journal Year:
2023,
Volume and Issue:
149, P. 105167 - 105167
Published: April 11, 2023
Noradrenergic
and
cholinergic
systems
are
among
the
most
vulnerable
brain
in
neuropsychiatric
diseases
of
ageing,
including
Alzheimer's
disease,
Parkinson's
Lewy
body
dementia,
progressive
supranuclear
palsy.
As
these
fail,
they
contribute
directly
to
many
characteristic
cognitive
psychiatric
symptoms.
However,
their
contribution
symptoms
is
not
sufficiently
understood,
pharmacological
interventions
targeting
noradrenergic
have
met
with
mixed
success.
Part
challenge
complex
neurobiology
systems,
operating
across
multiple
timescales,
non-linear
changes
adult
lifespan
disease
course.
We
address
challenges
a
detailed
review
outlining
roles
cognition
behaviour,
how
influence
disease.
By
bridging
levels
analysis,
we
highlight
opportunities
for
improving
drug
therapies
pursuing
personalised
medicine
strategies.
Trends in Neurosciences,
Journal Year:
2023,
Volume and Issue:
47(2), P. 92 - 105
Published: Dec. 14, 2023
Predictive
processing
models
posit
that
brains
constantly
attempt
to
predict
their
sensory
inputs.
Prediction
errors
signal
when
these
predictions
are
incorrect
and
thought
be
instructive
signals
drive
corrective
plasticity.
Recent
findings
support
the
idea
locus
coeruleus
(LC)
-
a
brain-wide
neuromodulatory
system
several
types
of
prediction
error.
I
discuss
how
proposing
LC
global
model
failures:
instances
where
about
world
strongly
violated.
Focusing
on
cortex,
explore
utility
this
in
learning
rate
control,
circuit
may
compute
signal,
view
aid
our
understanding
neurodivergence.
Frontiers in Systems Neuroscience,
Journal Year:
2023,
Volume and Issue:
17
Published: April 17, 2023
Anxiety
disorders
are
the
most
common
class
of
mental
illness
in
U.S.,
affecting
40
million
individuals
annually.
is
an
adaptive
response
to
a
stressful
or
unpredictable
life
event.
Though
evolutionarily
thought
aid
survival,
excess
intensity
duration
anxiogenic
can
lead
plethora
adverse
symptoms
and
cognitive
dysfunction.
A
wealth
data
has
implicated
medial
prefrontal
cortex
(mPFC)
regulation
anxiety.
Norepinephrine
(NE)
crucial
neuromodulator
arousal
vigilance
believed
be
responsible
for
many
anxiety
disorders.
NE
synthesized
locus
coeruleus
(LC),
which
sends
major
noradrenergic
inputs
mPFC.
Given
unique
properties
LC-mPFC
connections
heterogeneous
subpopulation
neurons
known
involved
regulating
anxiety-like
behaviors,
likely
modulates
PFC
function
cell-type
circuit-specific
manner.
In
working
memory
stress
response,
follows
inverted-U
model,
where
overly
high
low
release
associated
with
sub-optimal
neural
functioning.
contrast,
based
on
current
literature
review
individual
contributions
disorders,
we
propose
model
level-
adrenergic
receptor-dependent,
NE-PFC
modulation
Further,
advent
new
techniques
measure
unprecedented
spatial
temporal
resolution
will
significantly
help
us
understand
how
Cell Reports,
Journal Year:
2023,
Volume and Issue:
42(6), P. 112574 - 112574
Published: June 1, 2023
Understanding
cortical
function
requires
studying
multiple
scales:
molecular,
cellular,
circuit,
and
behavioral.
We
develop
a
multiscale,
biophysically
detailed
model
of
mouse
primary
motor
cortex
(M1)
with
over
10,000
neurons
30
million
synapses.
Neuron
types,
densities,
spatial
distributions,
morphologies,
biophysics,
connectivity,
dendritic
synapse
locations
are
constrained
by
experimental
data.
The
includes
long-range
inputs
from
seven
thalamic
regions
noradrenergic
inputs.
Connectivity
depends
on
cell
class
depth
at
sublaminar
resolution.
accurately
predicts
in
vivo
layer-
cell-type-specific
responses
(firing
rates
LFP)
associated
behavioral
states
(quiet
wakefulness
movement)
manipulations
(noradrenaline
receptor
blockade
thalamus
inactivation).
generate
mechanistic
hypotheses
underlying
the
observed
activity
analyzed
low-dimensional
population
latent
dynamics.
This
quantitative
theoretical
framework
can
be
used
to
integrate
interpret
M1
data
sheds
light
multiscale
dynamics
several
conditions
behaviors.
