How
memories
of
past
events
influence
behavior
is
a
key
question
in
neuroscience.
The
major
associative
learning
center
Drosophila,
the
mushroom
body
(MB),
communicates
to
rest
brain
through
output
neurons
(MBONs).
While
21
MBON
cell
types
have
their
dendrites
confined
small
compartments
MB
lobes,
analysis
EM
connectomes
revealed
presence
an
additional
14
that
are
atypical
having
dendritic
input
both
within
lobes
and
adjacent
regions.
Genetic
reagents
for
manipulating
MBONs
experimental
data
on
functions
been
lacking.
In
this
report
we
describe
new
cell-type-specific
GAL4
drivers
many
MBONs,
including
majority
extend
collection
driver
lines
previously
generated
(Aso
et
al.,
2014a;
Aso
2016;
2019).
Using
these
genetic
reagents,
conducted
optogenetic
activation
screening
examine
ability
drive
behaviors
learning.
These
provide
important
tools
study
complex
Drosophila.
The
neural
circuits
responsible
for
animal
behavior
remain
largely
unknown.
We
summarize
new
methods
and
present
the
circuitry
of
a
large
fraction
brain
fruit
fly
Drosophila
melanogaster
.
Improved
include
procedures
to
prepare,
image,
align,
segment,
find
synapses
in,
proofread
such
data
sets.
define
cell
types,
refine
computational
compartments,
provide
an
exhaustive
atlas
examples
many
them
novel.
detailed
consisting
neurons
their
chemical
most
central
brain.
make
public
simplify
access,
reducing
effort
needed
answer
circuit
questions,
linking
defined
by
our
analysis
with
genetic
reagents.
Biologically,
we
examine
distributions
connection
strengths,
motifs
on
different
scales,
electrical
consequences
compartmentalization,
evidence
that
maximizing
packing
density
is
important
criterion
in
evolution
fly’s
Making
inferences
about
the
computations
performed
by
neuronal
circuits
from
synapse-level
connectivity
maps
is
an
emerging
opportunity
in
neuroscience.
The
mushroom
body
(MB)
well
positioned
for
developing
and
testing
such
approach
due
to
its
conserved
architecture,
recently
completed
dense
connectome,
extensive
prior
experimental
studies
of
roles
learning,
memory,
activity
regulation.
Here,
we
identify
new
components
MB
circuit
Drosophila,
including
visual
input
output
neurons
(MBONs)
with
direct
connections
descending
neurons.
We
find
unexpected
structure
sensory
inputs,
transfer
information
different
modalities
MBONs,
modulation
that
dopaminergic
(DANs).
provide
insights
into
circuitry
used
integrate
outputs,
between
central
complex
inputs
DANs,
feedback
MBONs.
Our
results
a
foundation
further
theoretical
work.
To
analyse
neuron
data
at
scale,
neuroscientists
expend
substantial
effort
reading
documentation,
installing
dependencies
and
moving
between
analysis
visualisation
environments.
facilitate
this,
we
have
developed
a
suite
of
interoperable
open-source
R
packages
called
the
natverse.
The
natverse
allows
users
to
read
local
remote
data,
perform
popular
analyses
including
clustering
graph-theoretic
neuronal
branching.
Unlike
most
tools,
enables
comparison
across
many
neurons
morphology
connectivity
after
imaging
or
co-registration
within
common
template
space.
also
transformations
different
spaces
modalities.
We
demonstrate
tools
that
integrate
vast
majority
Cell,
Год журнала:
2024,
Номер
187(10), С. 2574 - 2594.e23
Опубликована: Май 1, 2024
High-resolution
electron
microscopy
of
nervous
systems
has
enabled
the
reconstruction
synaptic
connectomes.
However,
we
do
not
know
sign
for
each
connection
(i.e.,
whether
a
is
excitatory
or
inhibitory),
which
implied
by
released
transmitter.
We
demonstrate
that
artificial
neural
networks
can
predict
transmitter
types
presynapses
from
micrographs:
network
trained
to
six
transmitters
(acetylcholine,
glutamate,
GABA,
serotonin,
dopamine,
octopamine)
achieves
an
accuracy
87%
individual
synapses,
94%
neurons,
and
91%
known
cell
across
D.
melanogaster
whole
brain.
visualize
ultrastructural
features
used
prediction,
discovering
subtle
but
significant
differences
between
phenotypes.
also
analyze
distributions
brain
find
neurons
develop
together
largely
express
only
one
fast-acting
GABA).
hope
our
publicly
available
predictions
act
as
accelerant
neuroscientific
hypothesis
generation
fly.
Nature,
Год журнала:
2023,
Номер
617(7962), С. 777 - 784
Опубликована: Апрель 26, 2023
Associating
multiple
sensory
cues
with
objects
and
experience
is
a
fundamental
brain
process
that
improves
object
recognition
memory
performance.
However,
neural
mechanisms
bind
features
during
learning
augment
expression
are
unknown.
Here
we
demonstrate
multisensory
appetitive
aversive
in
Drosophila.
Combining
colours
odours
improved
performance,
even
when
each
modality
was
tested
alone.
Temporal
control
of
neuronal
function
revealed
visually
selective
mushroom
body
Kenyon
cells
(KCs)
to
be
required
for
enhancement
both
visual
olfactory
after
training.
Voltage
imaging
head-fixed
flies
showed
binds
activity
between
streams
modality-specific
KCs
so
unimodal
input
generates
multimodal
response.
Binding
occurs
regions
the
KC
axons,
which
receive
valence-relevant
dopaminergic
reinforcement,
propagated
downstream.
Dopamine
locally
releases
GABAergic
inhibition
permit
specific
microcircuits
within
KC-spanning
serotonergic
neurons
as
an
excitatory
bridge
previously
'modality-selective'
streams.
Cross-modal
binding
thereby
expands
representing
engram
into
those
other.
This
broadening
performance
permits
single
feature
retrieve
experience.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 18, 2024
Vision
provides
animals
with
detailed
information
about
their
surroundings,
conveying
diverse
features
such
as
color,
form,
and
movement
across
the
visual
scene.
Computing
these
parallel
spatial
requires
a
large
network
of
neurons,
that
in
distant
flies
humans,
regions
comprise
half
brain's
volume.
These
brain
often
reveal
remarkable
structure-function
relationships,
neurons
organized
along
maps
shapes
directly
relate
to
roles
processing.
To
unravel
stunning
diversity
complex
system,
careful
mapping
neural
architecture
matched
tools
for
targeted
exploration
circuitry
is
essential.
Here,
we
report
new
connectome
right
optic
lobe
from
male
Drosophila
central
nervous
system
FIB-SEM
volume
comprehensive
inventory
fly's
neurons.
We
developed
computational
framework
quantify
anatomy
establishing
basis
interpreting
how
vision.
By
integrating
this
analysis
connectivity
information,
neurotransmitter
identity,
expert
curation,
classified
~53,000
into
727
types,
which
are
systematically
described
named
first
time.
Finally,
share
an
extensive
collection
split-GAL4
lines
our
neuron
type
catalog.
Together,
set
data
unlock
possibilities
systematic
investigations
vision
Drosophila,
foundation
deeper
understanding
sensory
BMC Bioinformatics,
Год журнала:
2024,
Номер
25(1)
Опубликована: Март 15, 2024
Abstract
Background
Neuroscience
research
in
Drosophila
is
benefiting
from
large-scale
connectomics
efforts
using
electron
microscopy
(EM)
to
reveal
all
the
neurons
a
brain
and
their
connections.
To
exploit
this
knowledge
base,
researchers
relate
connectome’s
structure
neuronal
function,
often
by
studying
individual
neuron
cell
types.
Vast
libraries
of
fly
driver
lines
expressing
fluorescent
reporter
genes
sets
have
been
created
imaged
confocal
light
(LM),
enabling
targeting
for
experimentation.
However,
creating
line
driving
gene
expression
within
single
found
an
EM
connectome
remains
challenge,
as
it
typically
requires
identifying
pair
where
only
interest
expressed
both.
This
task
other
emerging
scientific
workflows
require
finding
similar
across
large
data
different
modalities.
Results
Here,
we
present
NeuronBridge,
web
application
easily
rapidly
putative
morphological
matches
between
We
describe
functionality
construction
NeuronBridge
service,
including
its
user-friendly
graphical
user
interface
(GUI),
extensible
model,
serverless
cloud
architecture,
massively
parallel
image
search
engine.
Conclusions
fills
critical
gap
workflow
used
hundreds
neuroscience
around
world.
offer
our
software
code,
open
APIs,
processed
integration
reuse,
provide
service
at
http://neuronbridge.janelia.org
.
In
most
animals,
a
relatively
small
number
of
descending
neurons
(DNs)
connect
higher
brain
centers
in
the
animal’s
head
to
circuits
and
motor
(MNs)
nerve
cord
body
that
effect
movement
limbs.
To
understand
how
signals
generate
behavior,
it
is
critical
these
pathways
are
organized
onto
MNs.
fly,
Drosophila
melanogaster
,
MNs
controlling
muscles
leg,
wing,
other
systems
reside
ventral
(VNC),
analogous
mammalian
spinal
cord.
companion
papers,
we
introduced
densely-reconstructed
connectome
Male
Adult
Nerve
Cord
(MANC,
Takemura
et
al.,
2023),
including
cell
type
developmental
lineage
annotation
(Marin
which
provides
complete
VNC
connectivity
at
synaptic
resolution.
Here,
present
first
look
organization
networks
connecting
DNs
based
on
this
new
information.
We
proofread
curated
all
ensure
accuracy
reliability,
then
systematically
matched
DN
axon
terminals
MN
dendrites
with
light
microscopy
data
link
their
morphology
inputs
or
muscle
targets.
report
both
broad
organizational
patterns
entire
network
fine-scale
analysis
selected
interest.
discover
direct
DN-MN
connections
infrequent
identify
communities
intrinsic
linked
control
different
systems,
putative
for
walking,
dorsal
flight
steering
power
generation,
intermediate
lower
tectulum
coordinated
action
wings
legs.
Our
generates
hypotheses
future
functional
experiments
and,
together
MANC
connectome,
empowers
others
investigate
richer
mechanistic
detail.