Animals
must
balance
the
urgent
need
to
find
food
during
starvation
with
critical
necessity
avoid
toxic
substances
ensure
their
survival.
In
Drosophila
,
specialized
Gustatory
Receptors
(GRs)
expressed
in
Receptor
Neurons
(GRNs)
are
for
distinguishing
between
nutritious
and
potentially
food.
GRNs
project
axons
from
taste
organs
Subesophageal
Zone
(SEZ)
Central
Brain
(CB)
of
where
gustatory
information
is
processed.
Although
roles
GRs
well-
documented,
processing
SEZ
remains
unclear.
To
better
understand
sensory
feeding
decision-making,
we
molecularly
characterized
first
layer
interneurons,
referred
as
Second
Order
(G2Ns),
which
receive
direct
input
GRNs.
Using
trans-synaptic
tracing
trans-
Tango,
cell
sorting,
bulk
RNAseq
under
fed
starved
conditions,
discovered
that
G2Ns
vary
based
on
molecular
profile
changes
fly’s
metabolic
state.
Further
data
analysis
has
revealed
a
pair
neurons
SEZ,
expressing
neuropeptide
Leucokinin
(SELK
neurons),
simultaneous
sensing
bitter
(potentially
toxic)
sweet
(nutritious)
information.
Additionally,
these
also
inputs
regarding
levels
fly.
These
results
highlight
novel
mechanism
regulation
integration.
Neural
circuits
carry
out
complex
computations
that
allow
animals
to
evaluate
food,
select
mates,
move
toward
attractive
stimuli,
and
away
from
threats.
In
insects,
the
subesophageal
zone
(SEZ)
is
a
brain
region
receives
gustatory,
pheromonal,
mechanosensory
inputs
contributes
control
of
diverse
behaviors,
including
feeding,
grooming,
locomotion.
Despite
its
importance
in
sensorimotor
transformations,
study
SEZ
has
been
hindered
by
limited
knowledge
underlying
diversity
neurons.
Here,
we
generate
collection
split-GAL4
lines
provides
precise
genetic
targeting
138
different
cell
types
adult
Drosophila
melanogaster,
comprising
approximately
one
third
all
We
characterize
single-cell
anatomy
these
neurons
find
they
cluster
morphology
into
six
supergroups
organize
discrete
anatomical
domains.
majority
local
interneurons
are
not
classically
polarized,
suggesting
rich
processing,
whereas
projection
tend
be
conveying
information
number
higher
regions.
This
insight
organization
generates
resources
will
facilitate
further
their
contributions
sensory
processing
behavior.
Transsynaptic
tracing
methods
are
crucial
tools
in
studying
neural
circuits.
Although
a
couple
of
anterograde
and
targeted
retrograde
tool
have
been
developed
Drosophila
melanogaster
,
there
is
still
need
for
an
unbiased,
user-friendly,
flexible
system.
Here,
we
describe
retro
-Tango,
method
transsynaptic,
circuit
manipulation
.
In
this
genetically
encoded
system,
ligand-receptor
interaction
at
the
synapse
triggers
intracellular
signaling
cascade
that
results
reporter
gene
expression
presynaptic
neurons.
Importantly,
panneuronal
elements
renders
versatile,
enabling
its
use
not
only
to
test
hypotheses
but
also
generate
them.
We
validate
-Tango
various
circuits
benchmark
it
by
comparing
our
findings
with
electron
microscopy
reconstruction
hemibrain.
Our
experiments
establish
as
key
neuroscience
research.
A
fundamental
question
in
sensory
processing
is
how
different
channels
of
input
are
processed
to
regulate
behavior.
Different
may
converge
onto
common
downstream
pathways
drive
the
same
behaviors,
or
they
activate
separate
distinct
behaviors.
We
investigated
this
Drosophila
bitter
taste
system,
which
contains
diverse
bitter-sensing
cells
residing
organs.
First,
we
optogenetically
activated
subsets
neurons
within
each
organ.
These
elicited
broad
and
highly
overlapping
behavioral
effects,
suggesting
that
pathways,
but
also
observed
differences
argue
for
biased
convergence.
Consistent
with
these
results,
transsynaptic
tracing
revealed
organs
connect
connectivity.
one
type
neuron
projects
higher
brain.
integrate
from
multiple
specific
taste-related
then
traced
circuits,
providing
first
glimpse
into
Together,
results
reveal
inputs
selectively
integrated
early
circuit,
enabling
pooling
information,
while
circuit
diverges
have
roles.
Taste
systems
encode
chemical
cues
that
drive
vital
behaviors.
We
have
elucidated
noncanonical
features
of
taste
coding
using
an
unconventional
kind
electrophysiological
analysis.
find
neurons
Drosophila
are
much
more
sensitive
than
previously
thought.
They
a
low
spontaneous
firing
frequency
depends
on
receptors.
dual
function
as
olfactory
neurons:
activated
by
most
tested
odorants,
including
N
,
-diethyl-
meta
-toluamide
(DEET),
at
distance.
DEET
can
also
inhibit
certain
neurons,
revealing
there
two
modes
response:
activation
and
inhibition.
characterize
OFF
responses
the
tastants
elicit
them
related
in
structure.
link
tastant
identity
to
behavior:
magnitude
response
elicited
correlated
with
egg
laying
behavior
it
elicited.
In
summary,
sensitivity
capacity
system
greater
known.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 19, 2023
Foraging
animals
must
balance
the
costs
of
exploring
their
surroundings
with
potential
benefits
finding
nutritional
resources.
Each
time
an
animal
encounters
a
food
source
it
decide
whether
to
initiate
feeding
or
continue
searching
for
potentially
better
options.
Experimental
evidence
and
patch
foraging
models
predict
that
this
decision
depends
on
both
state
density
available
resources
in
environment.
How
brain
integrates
such
internal
external
states
adapt
so-called
exploration-exploitation
trade-off
remains
poorly
understood.
We
use
video-based
tracking
show
Drosophila
regulates
engage
patches
based
travel
between
patches,
latter
being
measure
To
uncover
neuronal
basis
process,
we
performed
neurogenetic
silencing
screen
more
than
400
genetic
driver
lines
sparse
expression
patterns
fly
brain.
identified
population
neurons
central
complex
acts
as
key
regulator
patch.
manipulating
activity
these
alters
probability
engage,
is
modulated
by
protein
animal,
perturbs
ability
adjust
decisions
fly’s
patches.
Taken
together,
our
results
reveal
substrate
information
control
specific
decision,
therefore
provide
important
step
towards
mechanistic
explanation
cognitive
computations
resolve
cost-benefit
trade-offs.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 22, 2024
Summary
Knowing
how
neural
circuits
change
with
neuronal
plasticity
and
differ
between
individuals
is
important
to
fully
understand
behavior.
Connectomes
are
typically
assembled
using
electron
microscopy,
but
this
low
throughput
impractical
for
analyzing
or
mutations.
Here,
we
modified
the
trans
-Tango
genetic
circuit-tracing
technique
identify
neurons
synaptically
downstream
of
Drosophila
s-LNv
clock
neurons,
which
show
24hr
rhythms.
target
were
labeled
specifically
in
adult
flies
a
nuclear
reporter
gene,
facilitated
their
purification
then
single
cell
sequencing.
We
call
Tango-seq,
it
allows
transcriptomic
data
–
thus
identity
be
overlayed
on
top
anatomical
data.
found
that
s-LNvs
preferentially
make
synaptic
connections
subset
CNMa+
DN1p
these
likely
plastic
connections.
also
identified
mushroom
body
Kenyon
cells.
Tango-seq
should
useful
addition
connectomics
toolkit.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Фев. 12, 2025
Abstract
Our
sense
of
taste
is
critical
for
regulating
food
consumption.
The
fruit
fly
Drosophila
represents
a
highly
tractable
model
to
investigate
mechanisms
processing,
but
circuits
beyond
sensory
neurons
are
largely
unidentified.
Here,
we
use
whole-brain
connectome
the
organization
circuits.
We
trace
pathways
from
four
populations
that
detect
different
modalities
and
project
subesophageal
zone
(SEZ),
primary
region
brain.
find
second-order
primarily
located
within
SEZ
segregated
by
modality,
whereas
third-order
have
more
projections
outside
overlap
between
modalities.
Taste
out
innervate
regions
implicated
in
feeding,
olfactory
learning.
analyze
interconnections
pathways,
characterize
modality-dependent
differences
neuron
properties,
identify
other
types
inputs
onto
computational
simulations
relate
neuronal
connectivity
predicted
activity.
These
studies
provide
insight
into
architecture
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 6, 2025
ABSTRACT
Artificial
sweeteners
are
highly
sweet,
non-nutritive
compounds
that
have
become
increasingly
popular
over
recent
decades
despite
research
suggesting
their
consumption
has
unintended
consequences.
Specifically,
there
is
evidence
some
of
these
chemicals
interact
with
bitter
taste
receptors,
implying
likely
generate
complex
chemosensory
signals.
Here,
we
report
the
basic
sensory
characteristics
in
Drosophila
,
a
common
model
system
used
to
study
impacts
diet,
and
find
all
noncaloric
inhibited
appetitive
feeding
responses
at
higher
concentrations.
At
cellular
level,
found
sucralose
rebaudioside
A
co-activated
sweet
gustatory
receptor
neurons
(GRNs),
two
populations
reciprocally
impact
behavior,
while
aspartame
only
activated
cells.
We
assessed
behavioral
co-activation
low
concentrations
signal
high
aversion.
Finally,
silencing
GRNs
reduced
aversive
elicited
by
significantly
increased
behaviors.
Together,
conclude
artificial
more
than
“sweetness”
alone,
this
behaviorally
relevant
effects
on
may
help
flies
flexibly
respond
unique
compounds.
PLoS Genetics,
Год журнала:
2024,
Номер
20(3), С. e1011190 - e1011190
Опубликована: Март 14, 2024
A
population
of
neurons
interconnected
by
synapses
constitutes
a
neural
circuit,
which
performs
specific
functions
upon
activation.
It
is
essential
to
identify
both
anatomical
and
functional
entities
circuits
comprehend
the
components
processes
necessary
for
healthy
brain
function
changes
that
characterize
disorders.
To
date,
few
methods
are
available
study
these
two
aspects
circuit
simultaneously.
In
this
study,
we
developed
FLIPSOT,
or
labeling
individualized
postsynaptic
using
optogenetics
trans-
Tango.
FLIPSOT
uses
(1)
Tango
access
genetically,
(2)
optogenetic
approaches
activate
(FLIPSOTa)
inhibit
(FLIPSOTi)
in
random
sparse
manner,
(3)
fluorescence
markers
tagged
with
genes
visualize
neurons.
Therefore,
allows
presynaptic
driver
behavioral
individual
readily
applied
has
potential
be
adapted
use
mammalian
circuits.