Neuron,
Год журнала:
2024,
Номер
112(6), С. 942 - 958.e13
Опубликована: Янв. 22, 2024
Neurons
express
various
combinations
of
neurotransmitter
receptor
(NR)
subunits
and
receive
inputs
from
multiple
neuron
types
expressing
different
neurotransmitters.
Localizing
NR
to
specific
synaptic
has
been
challenging.
Here,
we
use
epitope-tagged
endogenous
subunits,
expansion
light-sheet
microscopy,
electron
microscopy
(EM)
connectomics
molecularly
characterize
synapses
in
Drosophila.
We
show
that
directionally
selective
motion-sensitive
neurons,
NRs
elaborated
a
highly
stereotyped
molecular
topography
with
localized
domains
receiving
cell-type-specific
inputs.
Developmental
studies
suggested
or
complexes
them
other
membrane
proteins
determine
patterns
In
support
this
model,
identify
transmembrane
protein
selectively
associated
subset
spatially
restricted
demonstrate
its
requirement
for
synapse
formation
through
genetic
analysis.
propose
mechanisms
regulate
the
precise
spatial
distribution
provide
cartography
specifying
connections
onto
dendrites.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 30, 2023
Abstract
Connections
between
neurons
can
be
mapped
by
acquiring
and
analyzing
electron
microscopic
(EM)
brain
images.
In
recent
years,
this
approach
has
been
applied
to
chunks
of
brains
reconstruct
local
connectivity
maps
that
are
highly
informative,
yet
inadequate
for
understanding
function
more
globally.
Here,
we
present
the
first
neuronal
wiring
diagram
a
whole
adult
brain,
containing
5×10
7
chemical
synapses
∼130,000
reconstructed
from
female
Drosophila
melanogaster
.
The
resource
also
incorporates
annotations
cell
classes
types,
nerves,
hemilineages,
predictions
neurotransmitter
identities.
Data
products
available
download,
programmatic
access,
interactive
browsing
made
interoperable
with
other
fly
data
resources.
We
show
how
derive
projectome,
map
projections
regions,
connectome.
demonstrate
tracing
synaptic
pathways
analysis
information
flow
inputs
(sensory
ascending
neurons)
outputs
(motor,
endocrine,
descending
neurons),
across
both
hemispheres,
central
optic
lobes.
Tracing
subset
photoreceptors
all
way
motor
illustrates
structure
uncover
putative
circuit
mechanisms
underlying
sensorimotor
behaviors.
technologies
open
ecosystem
FlyWire
Consortium
set
stage
future
large-scale
connectome
projects
in
species.
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.
Neuron,
Год журнала:
2023,
Номер
111(22), С. 3570 - 3589.e5
Опубликована: Ноя. 1, 2023
Efforts
are
ongoing
to
map
synaptic
wiring
diagrams,
or
connectomes,
understand
the
neural
basis
of
brain
function.
However,
chemical
synapses
represent
only
one
type
functionally
important
neuronal
connection;
in
particular,
extrasynaptic,
"wireless"
signaling
by
neuropeptides
is
widespread
and
plays
essential
roles
all
nervous
systems.
By
integrating
single-cell
anatomical
gene-expression
datasets
with
biochemical
analysis
receptor-ligand
interactions,
we
have
generated
a
draft
connectome
neuropeptide
C.
elegans
system.
This
network
characterized
high
connection
density,
extended
cascades,
autocrine
foci,
decentralized
topology,
large,
highly
interconnected
core
containing
three
constituent
communities
sharing
similar
patterns
input
connectivity.
Intriguingly,
several
key
hubs
little-studied
neurons
that
appear
specialized
for
peptidergic
neuromodulation.
We
anticipate
neuropeptidergic
will
serve
as
prototype
how
networks
neuromodulatory
organized.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июнь 27, 2023
Abstract
The
fruit
fly
Drosophila
melanogaster
combines
surprisingly
sophisticated
behaviour
with
a
highly
tractable
nervous
system.
A
large
part
of
the
fly’s
success
as
model
organism
in
modern
neuroscience
stems
from
concentration
collaboratively
generated
molecular
genetic
and
digital
resources.
As
presented
our
FlyWire
companion
paper
1
,
this
now
includes
first
full
brain
connectome
an
adult
animal.
Here
we
report
systematic
hierarchical
annotation
∼130,000-neuron
including
neuronal
classes,
cell
types
developmental
units
(hemilineages).
This
enables
any
researcher
to
navigate
huge
dataset
find
systems
neurons
interest,
linked
literature
through
Virtual
Fly
Brain
database
2
.
Crucially,
resource
4,552
types.
3,094
are
rigorous
consensus
validations
previously
proposed
“hemibrain”
3
In
addition,
propose
1,458
new
types,
arising
mostly
fact
that
spans
whole
brain,
whereas
hemibrain
derives
subvolume.
Comparison
showed
type
counts
strong
connections
were
largely
stable,
but
connection
weights
variable
within
across
animals.
Further
analysis
defined
simple
heuristics
for
interpretation:
stronger
than
10
unitary
synapses
or
providing
>1%
input
target
conserved.
Some
increased
variability
connectomes:
most
common
mushroom
body,
required
learning
memory,
is
almost
twice
numerous
hemibrain.
We
evidence
functional
homeostasis
adjustments
absolute
amount
excitatory
while
maintaining
excitation-inhibition
ratio.
Finally,
surprisingly,
about
one
third
could
not
yet
be
reliably
identified
connectome.
therefore
suggest
should
robust
inter-individual
variation,
namely
groups
cells
quantitatively
more
similar
different
other
same
brain.
Joint
connectomes
demonstrates
viability
utility
definition.
Our
work
defines
atlas
provides
both
intellectual
framework
open
source
toolchain
brain-scale
comparative
connectomics.
Journal of Neuroscience,
Год журнала:
2023,
Номер
43(34), С. 5989 - 5995
Опубликована: Авг. 23, 2023
The
brain
is
a
complex
system
comprising
myriad
of
interacting
elements,
posing
significant
challenges
in
understanding
its
structure,
function,
and
dynamics.
Network
science
has
emerged
as
powerful
tool
for
studying
such
intricate
systems,
offering
framework
integrating
multiscale
data
complexity.
Here,
we
discuss
the
application
network
study
brain,
addressing
topics
models
metrics,
connectome,
role
dynamics
neural
networks.
We
explore
opportunities
multiple
streams
transitions
from
development
to
healthy
function
disease,
potential
collaboration
between
neuroscience
communities.
underscore
importance
fostering
interdisciplinary
through
funding
initiatives,
workshops,
conferences,
well
supporting
students
postdoctoral
fellows
with
interests
both
disciplines.
By
uniting
communities,
can
develop
novel
network-based
methods
tailored
circuits,
paving
way
towards
deeper
functions.
Cell,
Год журнала:
2024,
Номер
187(3), С. 563 - 584
Опубликована: Фев. 1, 2024
Biology
spans
a
continuum
of
length
and
time
scales.
Individual
experimental
methods
only
glimpse
discrete
pieces
this
spectrum
but
can
be
combined
to
construct
more
holistic
view.
In
Review,
we
detail
the
latest
advancements
in
volume
electron
microscopy
(vEM)
cryo-electron
tomography
(cryo-ET),
which
together
visualize
biological
complexity
across
scales
from
organization
cells
large
tissues
molecular
details
inside
native
cellular
environments.
addition,
discuss
emerging
methodologies
for
integrating
three-dimensional
(3DEM)
imaging
with
multimodal
data,
including
fluorescence
microscopy,
mass
spectrometry,
single-particle
analysis,
AI-based
structure
prediction.
This
multifaceted
approach
fills
gaps
continuum,
providing
functional
context,
spatial
organization,
identity,
interactions.
We
conclude
perspective
on
incorporating
diverse
data
into
computational
simulations
that
further
bridge
extend
while
dimension
time.
