Mesolimbic
dopamine
encoding
of
non-contingent
rewards
and
reward-predictive
cues
has
been
well
established.
Considerable
debate
remains
over
how
mesolimbic
responds
to
aversion
in
the
context
aversive
conditioning.
Inconsistencies
may
arise
from
use
stimuli
that
are
transduced
along
different
neural
paths
relative
reward
or
conflation
responses
avoidance
aversion.
Here,
we
made
intraoral
infusions
sucrose
measured
behavioral
varied
changing
valence
sucrose.
Pairing
with
malaise
via
injection
lithium
chloride
(LiCl)
caused
development
a
conditioned
taste
(CTA),
which
rendered
typically
rewarding
upon
subsequent
re-exposure.
Following
CTA
formation,
suppressed
activity
ventral
tegmental
area
neurons
(VTADA)
nucleus
accumbens
(NAc)
release.
This
pattern
signaling
after
is
similar
innately
quinine
contrasts
when
it
was
novel
not
paired
LiCl.
Dopamine
were
negatively
correlated
reactivity
predicted
home
cage
preference.
Further,
scaled
strength
CTA,
increased
by
repeated
LiCl
pairings
weakened
through
extinction.
Thus,
findings
demonstrate
differential
same
stimulus
according
its
valence,
aligned
distinct
responses.
Head-fixed
behavioral
experiments
in
rodents
permit
unparalleled
experimental
control,
precise
measurement
of
behavior,
and
concurrent
modulation
neural
activity.
Here,
we
present
OHRBETS
(Open-Source
Rodent
Behavioral
Experimental
Training
System;
pronounced
'Orbitz'),
a
low-cost,
open-source
platform
hardware
software
to
flexibly
pursue
the
basis
variety
motivated
behaviors.
mice
tested
with
displayed
operant
conditioning
for
caloric
reward
that
replicates
core
phenotypes
observed
during
freely
moving
conditions.
also
permits
optogenetic
intracranial
self-stimulation
under
positive
or
negative
procedures
real-time
place
preference
like
assays.
In
multi-spout
brief-access
consumption
task,
licking
as
function
concentration
sucrose,
quinine,
sodium
chloride,
modulated
by
homeostatic
circadian
influences.
Finally,
highlight
functionality
OHRBETS,
measured
mesolimbic
dopamine
signals
task
display
strong
correlations
relative
solution
value
magnitude
consumption.
All
designs,
programs,
instructions
are
provided
online.
This
customizable
enables
replicable
consummatory
behaviors
can
be
incorporated
methods
perturb
record
dynamics
vivo.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июнь 25, 2024
Abstract
Nociceptin/orphanin-FQ
(N/OFQ)
is
a
recently
appreciated
critical
opioid
peptide
with
key
regulatory
functions
in
several
central
behavioral
processes
including
motivation,
stress,
feeding,
and
sleep.
The
functional
relevance
of
N/OFQ
action
the
mammalian
brain
remains
unclear
due
to
lack
high-resolution
approaches
detect
this
neuropeptide
appropriate
spatial
temporal
resolution.
Here
we
develop
characterize
NOPLight,
genetically
encoded
sensor
that
sensitively
reports
changes
endogenous
release.
We
characterized
affinity,
pharmacological
profile,
spectral
properties,
kinetics,
ligand
selectivity,
potential
interaction
intracellular
signal
transducers
NOPLight
vitro.
Its
functionality
was
established
acute
slices
by
exogeneous
application
chemogenetic
induction
release
from
PNOC
neurons.
In
vivo
studies
fibre
photometry
enabled
direct
recording
binding
exogenous
receptor
ligands,
as
well
detection
within
paranigral
ventral
tegmental
area
(pnVTA)
during
natural
behaviors
activation
summary,
show
here
can
be
used
dynamics
tissue
freely
behaving
animals.
Mesolimbic
dopamine
encoding
of
non-contingent
rewards
and
reward-predictive
cues
has
been
well
established.
Considerable
debate
remains
over
how
mesolimbic
responds
to
aversion
in
the
context
aversive
conditioning.
Inconsistencies
may
arise
from
use
stimuli
that
are
transduced
along
different
neural
paths
relative
reward
or
conflation
responses
avoidance
aversion.
Here,
we
made
intraoral
infusions
sucrose
measured
behavioral
varied
changing
valence
sucrose.
Pairing
with
malaise
via
injection
lithium
chloride
(LiCl)
caused
development
a
conditioned
taste
(CTA),
which
rendered
typically
rewarding
upon
subsequent
re-exposure.
Following
CTA
formation,
suppressed
activity
ventral
tegmental
area
neurons
(VTA
DA
)
nucleus
accumbens
(NAc)
release.
This
pattern
signaling
after
is
similar
innately
quinine
contrasts
when
it
was
novel
not
paired
LiCl.
Dopamine
were
negatively
correlated
reactivity
predicted
home
cage
preference.
Further,
scaled
strength
CTA,
increased
by
repeated
LiCl
pairings
weakened
through
extinction.
Thus,
findings
demonstrate
differential
same
stimulus
according
its
valence,
aligned
distinct
responses.
SignificanceMicroprism-mediated
calcium
imaging
of
deep
brain
structures
allows
for
reliable
tracking
thousands
cells
across
days,
a
marked
improvement
compared
with
industry-standard
approaches
utilizing
gradient-index
(GRIN)
lenses.AimWe
aim
to
develop
method
record,
track,
and
functionally
characterize
cortical
subcortical
neurons
using
an
endoscopic
microprism
benchmark
the
performance
against
traditional
GRIN
lenses.ApproachTo
improve
visualization
throughput
ensembles,
we
developed
characterized
protocol
implant
microprism.
We
performed
two-photon
through
microprisms
yield,
cell
quality,
optical
characteristics
lenses.ResultsWe
found
that
our
can
stably
isolate
track
active
days
weeks.
This
high-throughput
approach
facilitates
longitudinal
functional
characterization
large
groups
neural
ensembles
in
vivo
structures.
produces
high
fidelity
trackable
superior
resolution
quality
higher
spatial
precision
when
lenses.ConclusionsThe
technique
represents
significant
neuronal
ensemble
dynamics
within
tissues.
eNeuro,
Год журнала:
2025,
Номер
12(1), С. ENEURO.0364 - 24.2024
Опубликована: Янв. 1, 2025
The
study
of
the
neural
circuitry
underlying
complex
mammalian
decision-making,
particularly
cognitive
flexibility,
is
critical
for
understanding
psychiatric
disorders.
To
test
as
well
potentially
other
decision-making
paradigms
involving
multimodal
sensory
perception,
we
developed
FlexRig,
an
open-source,
modular
behavioral
platform
use
in
head-fixed
mice.
FlexRig
enables
administration
tasks
relying
upon
olfactory,
somatosensory,
and/or
auditory
cues
and
employing
left
right
licking
a
behavior
readout
reward
delivery
mechanism.
includes
hardware
software
components
that
are
customizable,
scalable,
portable,
supporting
variety
assays.
Using
established
task
to
model
attentional
set-shifting,
offering
new
tool
neuroscience
research
enhances
capacity
investigation
processes
their
substrates,
with
broad
applications
translational
neuroscience.
eNeuro,
Год журнала:
2025,
Номер
12(4), С. ENEURO.0457 - 24.2025
Опубликована: Апрель 1, 2025
Perceptual
decision-making
describes
the
process
of
selecting
an
appropriate
action
based
on
sensory
information
present
in
immediate
environment
and
is
hence
omnipresent
factor
life
animals.
In
preclinical
research,
a
widespread
approach
to
study
neuronal
correlates
perceptual
record
(and
manipulate)
activity
head-fixed
mice
performing
behavioral
tasks.
contrast
technologies
used
record/manipulate
activity,
standardization
training
generally
neglected,
circumstance
that
particularly
true
for
tasks
involving
auditory
stimuli.
Here,
we
DMC-Behavior
Platform,
open-source,
cost-efficient
framework
Combining
Platform
with
strategies
manipulate
offers
many
opportunities
test
hypotheses
underpinnings
cognitive
processes.
We
demonstrate
utility
platform
by
variants
three
commonly
decision-making:
detection,
Go/NoGo,
two-alternative
forced
choice
task.
The
presented
work
establishes
seamless
integration
synchronization
external
devices
task-related,
nontask-related
variables.
Our
provides
valuable
tool
more
standardized
reproducible
investigations
into
circuits
underlying
auditory-guided
decision-making.
eNeuro,
Год журнала:
2025,
Номер
12(4), С. ENEURO.0038 - 25.2025
Опубликована: Апрель 1, 2025
Investigation
of
neural
processes
underlying
motor
control
requires
behavioral
readouts
that
capture
the
richness
actions,
including
both
categorical
(choice-based)
information
and
execution
(kinematics).
We
present
an
open-source
platform
for
training
head-fixed
mice
combines
a
stationary
or
retractable
forelimb-based
joystick,
sound-presentation
system,
capacitive
lick
sensor,
water
reward
dispenser.
The
setup
allows
creation
multiple
paradigms,
two
which
are
highlighted
here:
two-alternative
forced-choice
auditory-motor
discrimination
paradigm
two-armed
bandit
value-based
decision-making
task.
In
paradigm,
learn
to
report
high-
low-frequency
tones
by
pushing
pulling
joystick.
push
pull
joystick
based
on
history
rewarded
trials.
addition
reporting
choices,
this
provides
rich
dataset
parameters
reflect
components
learning
decision
in
these
tasks.
These
kinematic
(including
speed
displacement,
Fréchet
similarity
trajectories,
tortuosity,
angular
standard
deviation,
movement
vigor)
provide
key
additional
insights
into
choices
not
as
readily
assessed
other
paradigms.
system's
flexibility
task
design,
readout,
ease
construction
represent
advance
compared
with
currently
available
manipulandum
tasks
mice.
detailed
schematics
constructing
protocols
using
hope
resource
is
adopted
neuroscientists
interested
mechanisms
sensorimotor
integration,
control,
choice
behavior.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 20, 2024
Abstract
Endogenous
neuropeptides
are
uniquely
poised
to
regulate
neuronal
activity
and
behavior
across
multiple
timescales.
Traditional
studies
ascribing
neuropeptide
contributions
lack
spatiotemporal
precision.
The
endogenous
opioid
dynorphin
is
highly
enriched
in
the
dorsal
striatum,
known
be
critical
for
regulating
goal-directed
behavior.
However,
locus,
precise
timescale,
or
functional
role
of
dyn-KOR
signaling
on
unknown.
Here,
we
report
that
local,
time-locked
release
from
dorsomedial
striatum
necessary
sufficient
using
a
suite
high
resolution
modern
approaches
including
vivo
two-photon
imaging,
biosensor
detection,
conditional
deletions
optogenetic
manipulations.
We
discovered
glutamatergic
axon
terminals
basolateral
amygdala
evoke
striatal
release,
resulting
retrograde
presynaptic
GPCR
inhibition
during
Collectively,
our
findings
isolate
causal
at
rapid
timescales,
subsequent
tuning
promoting
fundamental
behaviors.
