Biology & Philosophy,
Journal Year:
2023,
Volume and Issue:
39(1)
Published: Dec. 29, 2023
Abstract
Philosophers
examining
mechanistic
explanations
in
biology
have
identified
heuristic
strategies
scientists
use
discovering
mechanisms.
This
paper
examines
the
strategy
of
investigating
phylogenetically
distant
model
organisms,
using
research
on
sleep
fruit
flies
as
an
example.
At
time
was
discovered
2000
next
to
nothing
known
about
mechanisms
regulating
and
what
they
could
reveal
those
us.
One
relatively
straightforward
line
focused
homologous
genes
humans,
understand
roles
their
homologs
played
controlling
But
other
a
higher
level
organization—the
neural
networks
involved
homeostatic
circadian
control
sleep.
raises
puzzle—given
that
fly
vertebrate
brains
are
organized
very
differently,
how
regulation
serve
informative
sleep?
I
argue
basic
design
such
can
be
conserved
even
composition
mechanism
changes
researchers
hope
designs
deciphered
models
for
understanding
humans.
The
central
complex
(CX)
plays
a
key
role
in
many
higher-order
functions
of
the
insect
brain
including
navigation
and
activity
regulation.
Genetic
tools
for
manipulating
individual
cell
types,
knowledge
what
neurotransmitters
neuromodulators
they
express,
will
be
required
to
gain
mechanistic
understanding
how
these
are
implemented.
We
generated
characterized
split-GAL4
driver
lines
that
express
or
small
subsets
about
half
CX
types.
surveyed
neuropeptide
receptor
expression
using
fluorescent
situ
hybridization.
About
neuropeptides
we
examined
were
expressed
only
few
cells,
while
rest
dozens
hundreds
cells.
Neuropeptide
receptors
more
broadly
at
lower
levels.
Using
our
GAL4
drivers
mark
found
51
85
types
least
one
21
multiple
neuropeptides.
Surprisingly,
all
co-expressed
molecule
neurotransmitter.
Finally,
used
identify
whose
activation
affects
sleep,
identified
other
link
circadian
clock
CX.
well-characterized
genetic
information
on
neurotransmitter
provide
should
enhance
studies
Current Biology,
Journal Year:
2023,
Volume and Issue:
33(17), P. 3660 - 3668.e4
Published: Aug. 7, 2023
The
needs
fulfilled
by
sleep
are
unknown,
though
the
effects
of
insufficient
manifold.
To
better
understand
how
need
to
is
sensed
and
discharged,
much
effort
has
gone
into
identifying
neural
circuits
involved
in
regulating
arousal,
especially
those
that
promote
sleep.
In
prevailing
models,
dorsal
fan-shaped
body
(dFB)
plays
a
central
role
this
process
fly
brain.
present
study
we
manipulated
various
properties
dFB
including
its
electrical
activity,
synaptic
output,
endogenous
gene
expression.
each
these
experimental
contexts
were
unable
identify
any
effect
on
could
be
unambiguously
mapped
dFB.
Furthermore,
found
evidence
phenotypes
previously
attributed
caused
genetic
manipulations
inadvertently
targeted
ventral
nerve
cord.
We
also
examined
expression
two
genes
whose
purported
have
been
functions
within
specific
subpopulation
neurons.
both
cases
little
no
expected
cells.
Collectively,
our
results
cast
doubt
hypothesis
promoting
Nature Neuroscience,
Journal Year:
2024,
Volume and Issue:
27(2), P. 359 - 372
Published: Jan. 23, 2024
The
sleep-wake
cycle
is
determined
by
circadian
and
sleep
homeostatic
processes.
However,
the
molecular
impact
of
these
processes
their
interaction
in
different
brain
cell
populations
are
unknown.
To
fill
this
gap,
we
profiled
single-cell
transcriptome
adult
Drosophila
brains
across
four
times.
We
show
type-specific
transcriptomic
changes,
with
glia
displaying
largest
variation.
Glia
also
among
few
types
whose
gene
expression
correlates
both
homeostat
clock.
drive
level
affect
clock
regulators
glia,
disrupting
genes
specifically
impairs
rebound
after
deprivation.
These
findings
provide
a
comprehensive
view
effects
on
distinct
an
entire
animal
reveal
as
site
two
to
determine
dynamics.
The
central
complex
(CX)
plays
a
key
role
in
many
higher-order
functions
of
the
insect
brain
including
navigation
and
activity
regulation.
Genetic
tools
for
manipulating
individual
cell
types,
knowledge
what
neurotransmitters
neuromodulators
they
express,
will
be
required
to
gain
mechanistic
understanding
how
these
are
implemented.
We
generated
characterized
split-GAL4
driver
lines
that
express
or
small
subsets
about
half
CX
types.
surveyed
neuropeptide
receptor
expression
using
fluorescent
situ
hybridization.
About
neuropeptides
we
examined
were
expressed
only
few
cells,
while
rest
dozens
hundreds
cells.
Neuropeptide
receptors
more
broadly
at
lower
levels.
Using
our
GAL4
drivers
mark
found
51
85
types
least
one
21
multiple
neuropeptides.
Surprisingly,
all
co-expressed
neurotransmitter.
Finally,
used
identify
whose
activation
affects
sleep,
identified
other
link
circadian
clock
CX.
well-characterized
genetic
information
on
neurotransmitter
provide
should
enhance
studies
Science,
Journal Year:
2024,
Volume and Issue:
385(6716), P. 1459 - 1465
Published: Sept. 26, 2024
Sleep
is
regulated
by
homeostatic
processes,
yet
the
biological
basis
of
sleep
pressure
that
accumulates
during
wakefulness,
triggers
sleep,
and
dissipates
remains
elusive.
We
explored
a
causal
relationship
between
cellular
synaptic
strength
electroencephalography
delta
power
indicating
macro-level
developing
theoretical
framework
molecular
tool
to
manipulate
strength.
The
mathematical
model
predicted
increased
promotes
neuronal
“down
state”
raises
power.
Our
(synapse-targeted
chemically
induced
translocation
Kalirin-7,
SYNCit-K),
which
induces
dendritic
spine
enlargement
potentiation
through
protein
demonstrated
excitatory
neurons
in
prefrontal
cortex
(PFC)
increases
nonrapid
eye
movement
amounts
Thus,
PFC
dictates
mammals.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 22, 2024
The
central
complex
(CX)
plays
a
key
role
in
many
higher-order
functions
of
the
insect
brain
including
navigation
and
activity
regulation.
Genetic
tools
for
manipulating
individual
cell
types,
knowledge
what
neurotransmitters
neuromodulators
they
express,
will
be
required
to
gain
mechanistic
understanding
how
these
are
implemented.
We
generated
characterized
split-GAL4
driver
lines
that
express
or
small
subsets
about
half
CX
types.
surveyed
neuropeptide
receptor
expression
using
fluorescent
Journal of Neuroscience,
Journal Year:
2024,
Volume and Issue:
44(33), P. e2377232024 - e2377232024
Published: June 27, 2024
To
visualize
the
cellular
and
subcellular
localization
of
neuromodulatory
G-protein–coupled
receptors
in
Drosophila
,
we
implement
a
molecular
strategy
recently
used
to
add
epitope
tags
ionotropic
at
their
endogenous
loci.
Leveraging
evolutionary
conservation
identify
sites
more
likely
permit
insertion
tag,
generated
constitutive
conditional
tagged
alleles
for
5-HT1A
5-HT2A
5-HT2B
Oct
β
1R
2R
two
isoforms
OAMB
mGluR
.
The
allow
restricted
expression
receptor
specific
cell
types,
an
option
not
available
any
previous
reagents
label
these
proteins.
We
show
patterns
female
brains
that
localize
mushroom
bodies
(MBs)
central
complex,
respectively,
as
predicted
by
roles
sleep.
By
contrast,
unexpected
enrichment
Octβ1R
complex
nerve
terminals
lobular
columnar
cells
visual
system
suggest
new
hypotheses
about
functions
sites.
Using
additional
allele
serotonin
transporter,
marker
serotonergic
tracts,
demonstrate
diverse
spatial
relationships
between
postsynaptic
5-HT
presynaptic
neurons,
consistent
with
importance
both
synaptic
volume
transmission.
Finally,
use
it
localizes
distinct
within
MBs
Kenyon
autoreceptor.
The
central
complex
(CX)
plays
a
key
role
in
many
higher-order
functions
of
the
insect
brain
including
navigation
and
activity
regulation.
Genetic
tools
for
manipulating
individual
cell
types,
knowledge
what
neurotransmitters
neuromodulators
they
express,
will
be
required
to
gain
mechanistic
understanding
how
these
are
implemented.
We
generated
characterized
split-GAL4
driver
lines
that
express
or
small
subsets
about
half
CX
types.
surveyed
neuropeptide
receptor
expression
using
fluorescent
situ
hybridization.
About
neuropeptides
we
examined
were
expressed
only
few
cells,
while
rest
dozens
hundreds
cells.
Neuropeptide
receptors
more
broadly
at
lower
levels.
Using
our
GAL4
drivers
mark
found
51
85
types
least
one
21
multiple
neuropeptides.
Surprisingly,
all
co-expressed
neurotransmitter.
Finally,
used
identify
whose
activation
affects
sleep,
identified
other
link
circadian
clock
CX.
well-characterized
genetic
information
on
neurotransmitter
provide
should
enhance
studies
The
central
complex
(CX)
plays
a
key
role
in
many
higher-order
functions
of
the
insect
brain
including
navigation
and
activity
regulation.
Genetic
tools
for
manipulating
individual
cell
types,
knowledge
what
neurotransmitters
neuromodulators
they
express,
will
be
required
to
gain
mechanistic
understanding
how
these
are
implemented.
We
generated
characterized
split-GAL4
driver
lines
that
express
or
small
subsets
about
half
CX
types.
surveyed
neuropeptide
receptor
expression
using
fluorescent
situ
hybridization.
About
neuropeptides
we
examined
were
expressed
only
few
cells,
while
rest
dozens
hundreds
cells.
Neuropeptide
receptors
more
broadly
at
lower
levels.
Using
our
GAL4
drivers
mark
found
51
85
types
least
one
21
multiple
neuropeptides.
Surprisingly,
all
co-expressed
molecule
neurotransmitter.
Finally,
used
identify
whose
activation
affects
sleep,
identified
other
link
circadian
clock
CX.
well-characterized
genetic
information
on
neurotransmitter
provide
should
enhance
studies
Nature Neuroscience,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 21, 2025
Abstract
Homeostatic
processes,
including
sleep,
are
critical
for
brain
function.
Here
we
identify
astrocyte-like
glia
(or
astrocytes,
AL)
and
ensheathing
(EG),
the
two
major
classes
of
that
arborize
inside
brain,
as
brain-wide,
locally
acting
homeostats
short,
naturally
occurring
rest
sleep
bouts
Drosophila
,
show
a
subset
neurons
in
fan-shaped
body
encodes
feeding
homeostasis.
We
metabolic
gas
carbon
dioxide,
changes
pH
behavioral
activity
all
induce
long-lasting
calcium
responses
EG
AL,
levels
both
types
circadian
modulation.
The
homeostatic
dynamics
these
can
be
modeled
based
on
behavior.
Additionally,
local
optogenetic
activation
AL
or
is
sufficient
to
rest.
Together,
results
suggest
glial
controllers
activity,
thus
establishing
link
between
metabolism,
sleep.