Insulin
plays
a
critical
role
in
maintaining
metabolic
homeostasis.
Since
demands
are
highly
dynamic,
insulin
release
needs
to
be
constantly
adjusted.
These
adjustments
mediated
by
different
pathways,
most
prominently
the
blood
glucose
level,
but
also
feedforward
signals
from
motor
circuits
and
neuromodulatory
systems.
Here,
we
analyze
how
inputs
control
activity
of
main
source
Drosophila
–
population
Insulin-Producing
Cells
(IPCs)
located
brain.
IPCs
functionally
analogous
mammalian
pancreatic
beta
cells,
their
location
makes
them
accessible
for
vivo
recordings
intact
animals.
We
characterized
functional
using
single-nucleus
RNA
sequencing
analysis,
anatomical
receptor
expression
mapping,
connectomics,
an
optogenetics-based
‘in-trinsic
pharmacology’
approach.
Our
results
show
that
IPC
expresses
variety
receptors
neuromodulators
classical
neurotransmitters.
Interestingly,
exhibit
heterogeneous
profiles,
suggesting
can
modulated
differentially.
This
is
supported
electrophysiological
IPCs,
which
performed
while
activating
populations
modulatory
neurons.
analysis
revealed
some
have
effects
on
activity,
such
they
inhibit
one
subset
exciting
another.
Monitoring
calcium
across
uncovered
these
responses
occur
simultaneously.
Certain
shifted
towards
excited
state,
others
it
inhibition.
Taken
together,
provide
comprehensive,
multi-level
neuromodulation
insulinergic
system
.
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: July 5, 2021
Abstract
Feeding
decisions
are
fundamental
to
survival,
and
decision
making
is
often
disrupted
in
disease.
Here,
we
show
that
neural
activity
a
small
population
of
neurons
projecting
the
fan-shaped
body
higher-order
central
brain
region
Drosophila
represents
food
choice
during
sensory
conflict.
We
found
deprived
flies
made
tradeoffs
between
appetitive
aversive
values
food.
identified
an
upstream
neuropeptidergic
dopaminergic
network
relays
internal
state
other
decision-relevant
information
specific
subset
neurons.
These
were
strongly
inhibited
by
taste
rejected
choice,
suggesting
they
encode
behavioral
choice.
Our
findings
reveal
responses
choices
determined
not
only
quality,
but
also
previous
experience
(including
outcome)
hunger
state,
which
integrated
before
relay
downstream
motor
circuits
for
implementation.
Cellular and Molecular Life Sciences,
Journal Year:
2022,
Volume and Issue:
79(3)
Published: March 1, 2022
Neuropeptides
are
the
most
diverse
messenger
molecules
in
metazoans
and
involved
regulation
of
daily
physiology
a
wide
array
behaviors.
Some
neuropeptides
their
cognate
receptors
structurally
functionally
well
conserved
over
evolution
bilaterian
animals.
Among
these
peptides
related
to
gastrin
cholecystokinin
(CCK).
In
mammals,
CCK
is
produced
by
intestinal
endocrine
cells
brain
neurons,
regulates
gall
bladder
contractions,
pancreatic
enzyme
secretion,
gut
functions,
satiety
food
intake.
Additionally,
plays
important
roles
neuromodulation
several
circuits
that
regulate
reward,
anxiety,
aggression
sexual
behavior.
invertebrates,
CCK-type
(sulfakinins,
SKs)
are,
with
few
exceptions,
neurons
only.
Common
among
invertebrates
SKs
mediate
ingestion
variety
mechanisms.
Also
secretion
digestive
enzymes
has
been
reported.
Studies
genetically
tractable
fly
Drosophila
have
advanced
our
understanding
SK
signaling
mechanisms
feeding,
but
also
gustatory
sensitivity,
locomotor
activity,
reproductive
A
set
eight
SK-expressing
competing
males,
they
integrate
internal
state
external
stimuli
diminish
sex
drive
increase
aggression.
The
same
sugar
gustation,
induce
reduce
feeding.
Although
functional
CCK/SK
appear
between
available
data
suggest
underlying
differ.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Sept. 13, 2023
The
circadian
clock
and
its
output
pathways
play
a
pivotal
role
in
optimizing
daily
processes.
To
obtain
novel
insights
into
how
diverse
rhythmic
physiology
behaviors
are
orchestrated,
we
have
generated
the
first
comprehensive
connectivity
map
of
an
animal
using
Drosophila
FlyWire
brain
connectome.
Intriguingly,
identified
additional
dorsal
neurons,
thus
showing
that
network
contains
∼240
instead
150
neurons.
We
also
revealed
extensive
contralateral
synaptic
within
discovered
indirect
light
input
to
Interestingly,
observed
sparse
monosynaptic
between
neurons
down-stream
higher-order
centers
neurosecretory
cells
known
regulate
behavior
physiology.
Therefore,
integrated
single-cell
transcriptomics
receptor
mapping
decipher
putative
paracrine
peptidergic
signaling
by
Our
analyses
neuropeptides
expressed
suggest
significantly
enriches
interconnectivity
network.
Insects
have
evolved
a
variety
of
neurohormones
that
enable
them
to
maintain
their
nutrient
and
osmotic
homeostasis.
While
the
identities
functions
various
insect
metabolic
diuretic
hormones
been
well-established,
characterization
an
anti-diuretic
signaling
system
is
conserved
across
most
insects
still
lacking.
To
address
this,
here
we
characterized
ion
transport
peptide
(ITP)
in
Drosophila
.
The
ITP
gene
encodes
five
transcript
variants
which
generate
three
different
isoforms:
amidated
(ITPa)
two
ITP-like
(ITPL1
ITPL2)
isoforms.
Using
combination
anatomical
mapping
single-cell
transcriptome
analyses,
comprehensively
expression
all
isoforms
nervous
peripheral
tissues.
Our
analyses
reveal
widespread
Moreover,
show
ITPa
released
during
dehydration
recombinant
inhibits
peptide-induced
renal
tubule
secretion
ex
vivo
,
thus
confirming
its
role
as
hormone.
phylogenetic-driven
approach
assay,
identified
functionally
Gyc76C,
membrane
guanylate
cyclase,
elusive
receptor.
Thus,
knockdown
Gyc76C
tubules
abolishes
inhibitory
effect
on
hormone
secretion.
Extensive
reveals
it
highly
expressed
larval
adult
tissues
associated
with
osmoregulation
(renal
rectum)
homeostasis
(fat
body).
Consistent
this
expression,
impacts
tolerance
ionic
stresses,
whereas
specifically
fat
body
feeding,
behaviors.
We
also
complement
receptor
experiments
overexpression
neurons.
Interestingly,
ITPa-Gyc76C
pathways
deciphered
are
reminiscent
atrial
natriuretic
mammals.
Lastly,
utilized
connectomics
transcriptomics
identify
synaptic
paracrine
upstream
downstream
ITP-expressing
Taken
together,
our
systematic
establishes
tractable
decipher
how
small
set
neurons
integrates
diverse
inputs
orchestrate
systemic
Insulin
plays
a
critical
role
in
maintaining
metabolic
homeostasis.
Since
demands
are
highly
dynamic,
insulin
release
needs
to
be
constantly
adjusted.
These
adjustments
mediated
by
different
pathways,
most
prominently
the
blood
glucose
level,
but
also
feedforward
signals
from
motor
circuits
and
neuromodulatory
systems.
Here,
we
analyze
how
inputs
control
activity
of
main
source
Drosophila
–
population
Insulin-Producing
Cells
(IPCs)
located
brain.
IPCs
functionally
analogous
mammalian
pancreatic
beta
cells,
their
location
makes
them
accessible
for
vivo
recordings
intact
animals.
We
characterized
functional
using
single-nucleus
RNA
sequencing
analysis,
anatomical
receptor
expression
mapping,
connectomics,
an
optogenetics-based
‘in-trinsic
pharmacology’
approach.
Our
results
show
that
IPC
expresses
variety
receptors
neuromodulators
classical
neurotransmitters.
Interestingly,
exhibit
heterogeneous
profiles,
suggesting
can
modulated
differentially.
This
is
supported
electrophysiological
IPCs,
which
performed
while
activating
populations
modulatory
neurons.
analysis
revealed
some
have
effects
on
activity,
such
they
inhibit
one
subset
exciting
another.
Monitoring
calcium
across
uncovered
these
responses
occur
simultaneously.
Certain
shifted
towards
excited
state,
others
it
inhibition.
Taken
together,
provide
comprehensive,
multi-level
neuromodulation
insulinergic
system
.