bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 5, 2023
Abstract
The
function
of
neuronal
networks
is
determined
not
only
by
synaptic
connectivity
but
also
neuromodulatory
systems
that
broadcast
information
via
distributed
connections
and
volume
transmission.
To
understand
the
molecular
constraints
organize
signaling
in
telencephalon
adult
zebrafish
we
used
transcriptomics
additional
approaches
to
delineate
cell
types,
determine
their
phylogenetic
conservation,
map
expression
marker
genes
at
high
granularity.
combinatorial
GPCRs
type
markers
indicates
all
types
are
subject
modulation
multiple
monoaminergic
distinct
combinations
neuropeptides.
Individual
were
associated
with
(typically
>30)
expressed
a
few
diagnostic
levels,
suggesting
different
act
combination
albeit
unequal
weights.
These
results
provide
detailed
brain
areas
telencephalon,
identify
core
components
networks,
highlight
type-specificity
neuropeptides
GPCRs,
begin
decipher
logic
neuromodulation.
Nature,
Journal Year:
2023,
Volume and Issue:
623(7986), P. 406 - 414
Published: Nov. 1, 2023
Abstract
Establishing
how
neural
function
emerges
from
network
properties
is
a
fundamental
problem
in
neuroscience
1
.
Here,
to
better
understand
the
relationship
between
structure
and
of
nervous
system,
we
systematically
measure
signal
propagation
23,433
pairs
neurons
across
head
nematode
Caenorhabditis
elegans
by
direct
optogenetic
activation
simultaneous
whole-brain
calcium
imaging.
We
sign
(excitatory
or
inhibitory),
strength,
temporal
causal
direction
these
create
functional
atlas.
find
that
differs
model
predictions
are
based
on
anatomy.
Using
mutants,
show
extrasynaptic
signalling
not
visible
anatomy
contributes
this
difference.
identify
many
instances
dense-core-vesicle-dependent
signalling,
including
timescales
less
than
second,
evoke
acute
transients—often
where
no
wired
connection
exists
but
relevant
neuropeptides
receptors
expressed.
propose
that,
such
cases,
extrasynaptically
released
serve
similar
classical
neurotransmitters.
Finally,
our
measured
atlas
predicts
dynamics
spontaneous
activity
do
models
conclude
both
synaptic
drive
short
timescales,
measurements
evoked
crucial
for
interpreting
function.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Nov. 1, 2022
Summary
Neuropeptides
are
ancient,
widespread
signaling
molecules
that
underpin
almost
all
brain
functions.
They
constitute
a
broad
ligand-receptor
network,
mainly
by
binding
to
G
protein-coupled
receptors
(GPCRs).
However,
the
organization
of
peptidergic
network
and
roles
many
neuropeptides
remain
elusive,
as
our
insight
into
neuropeptide-receptor
interactions
is
limited
peptide
GPCRs
in
animal
models
humans
still
orphan
receptors.
Here
we
report
genome-wide
neuropeptide-GPCR
interaction
map
C.
elegans
.
By
reverse
pharmacology
screening
over
55,384
possible
interactions,
identify
461
cognate
peptide-GPCR
couples
uncover
with
specific
complex
combinatorial
encoded
across
within
single
genes.
These
provide
insights
neuropeptide
functions
evolution.
Combining
dataset
phylogenetic
analysis
supports
peptide-receptor
co-evolution
conservation
at
least
14
bilaterian
systems
This
resource
lays
foundation
for
system-wide
network.
Highlights
System-wide
deorphanizes
68
Discovery
pairs
additional
ligands
characterized
show
receptor
Peptide-GPCR
support
long-range
expansion
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: March 24, 2023
A
comprehensive
description
of
nervous
system
function,
and
sex
dimorphism
within,
is
incomplete
without
clear
assessment
the
diversity
its
component
cell
types,
neurons
glia.
C.
elegans
has
an
invariant
with
first
mapped
connectome
a
multi-cellular
organism
single-cell
atlas
neurons.
Here
we
present
single
nuclear
RNA-seq
evaluation
glia
across
entire
adult
system,
including
both
sexes.
Machine
learning
models
enabled
us
to
identify
sex-shared
sex-specific
glial
subclasses.
We
have
identified
validated
molecular
markers
in
silico
vivo
for
these
subcategories.
Comparative
analytics
also
reveals
previously
unappreciated
heterogeneity
anatomically
identical
between
within
sexes,
indicating
consequent
functional
heterogeneity.
Furthermore,
our
datasets
reveal
that
while
express
neuropeptide
genes,
they
lack
canonical
unc-31/CAPS-dependent
dense
core
vesicle
release
machinery.
Thus,
employ
alternate
neuromodulator
processing
mechanisms.
Overall,
this
atlas,
available
at
www.wormglia.org,
rich
insights
into
animal
Annual Review of Cell and Developmental Biology,
Journal Year:
2023,
Volume and Issue:
39(1), P. 45 - 65
Published: June 20, 2023
Myriad
mechanisms
have
evolved
to
adapt
changing
environments.
Environmental
stimuli
alter
organisms'
physiology
create
memories
of
previous
Whether
these
environmental
can
cross
the
generational
barrier
has
interested
scientists
for
centuries.
The
logic
passing
on
information
from
generation
is
not
well
understood.
When
it
useful
remember
ancestral
conditions,
and
when
might
be
deleterious
continue
respond
a
context
that
may
no
longer
exist?
key
found
in
understanding
conditions
trigger
long-lasting
adaptive
responses.
We
discuss
biological
systems
use
conditions.
Responses
spanning
different
timescales
employ
molecular
machineries
result
differences
duration
or
intensity
exposure.
Understanding
components
multigenerational
inheritance
underlying
beneficial
maladaptive
adaptations
fundamental
how
organisms
acquire
transmit
across
generations.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 5, 2024
SUMMARY
When
animals
are
infected
by
a
pathogen,
peripheral
sensors
of
infection
signal
to
the
brain
coordinate
set
adaptive
behavioral
changes
known
as
sickness
behaviors.
While
pathways
that
from
periphery
have
been
intensively
studied
in
recent
years,
how
central
circuits
reconfigured
elicit
behaviors
is
not
well
understood.
Here
we
find
neuromodulatory
systems
linked
stress
and
satiety
recruited
upon
drive
C.
elegans
.
Upon
chronic
bacterium
Pseudomonas
aeruginosa
PA14,
decrease
their
feeding
behavior,
then
display
reversible
bouts
quiescence,
eventually
die.
The
ALA
neuron
its
neuropeptides
FLP-7,
FLP-24,
NLP-8,
which
control
stress-induced
sleep
uninfected
animals,
promote
PA14-induced
reduction.
However,
neuropeptide
FLP-13
instead
acts
delay
quiescence
death
animals.
Cell-specific
genetic
perturbations
show
neurons
release
distinct
ALA.
A
brain-wide
imaging
screen
reveals
infection-induced
involves
ASI
DAF-7/TGF-beta,
satiety-induced
Our
results
suggest
common
neuromodulators
across
different
physiological
states,
acting
neural
sources
combinations
state-dependent
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: July 12, 2023
We
investigated
how
transmission
of
hunger-
and
satiety-promoting
neuropeptides,
NPY
αMSH,
is
integrated
at
the
level
intracellular
signaling
to
control
feeding.
Receptors
for
these
peptides
use
second
messenger
cAMP,
but
messenger's
spatiotemporal
dynamics
role
in
energy
balance
are
controversial.
show
that
AgRP
axon
stimulation
paraventricular
hypothalamus
evokes
probabilistic
spatially
restricted
release
triggers
stochastic
cAMP
decrements
downstream
MC4R-expressing
neurons
(PVH
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 25, 2023
ABSTRACT
Mapping
neurotransmitter
identities
to
neurons
is
key
understanding
information
flow
in
a
nervous
system.
It
also
provides
valuable
entry
points
for
studying
the
development
and
plasticity
of
neuronal
identity
features.
In
C.
elegans
system,
have
been
largely
assigned
by
expression
pattern
analysis
pathway
genes
that
encode
biosynthetic
enzymes
or
transporters.
However,
many
these
assignments
relied
on
multicopy
reporter
transgenes
may
lack
relevant
cis
-regulatory
therefore
not
provide
an
accurate
picture
usage.
We
analyzed
patterns
16
CRISPR/Cas9-engineered
knock-in
strains
all
main
types
neurotransmitters
(glutamate,
acetylcholine,
GABA,
serotonin,
dopamine,
tyramine,
octopamine)
both
hermaphrodite
male.
Our
reveals
novel
sites
systems
within
glia,
as
well
non-neural
cells.
The
resulting
atlas
defines
be
exclusively
neuropeptidergic,
substantially
expands
repertoire
capable
co-transmitting
multiple
neurotransmitters,
identifies
uptake
monoaminergic
neurotransmitters.
Furthermore,
we
observed
unusual
co-expression
synthesis
genes,
suggesting
existence
transmitters.
results
what
constitutes
most
extensive
whole-animal-wide
map
usage
date,
paving
way
better
communication
specification
.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: April 2, 2023
Animals
generate
a
wide
range
of
highly
coordinated
motor
outputs,
which
allows
them
to
execute
purposeful
behaviors.
Individual
neuron
classes
in
the
circuits
that
behavior
have
remarkable
capacity
for
flexibility,
as
they
exhibit
multiple
axonal
projections,
transmitter
systems,
and
modes
neural
activity.
How
these
multi-functional
properties
neurons
enable
generation
behaviors
remains
unknown.
Here
we
show
HSN
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 14, 2024
Abstract
The
nematode
worm
C.
elegans
provides
a
unique
opportunity
for
exploring
in
silico
data-driven
models
of
whole
nervous
system,
given
its
transparency
and
well-characterized
system
facilitating
wealth
measurement
data
from
wet-lab
experiments.
This
study
explores
the
scaling
properties
that
may
govern
learning
underlying
neural
dynamics
this
small
by
using
artificial
network
(ANN)
models.
We
investigate
accuracy
self-supervised
next
time-step
activity
prediction
as
function
For
scaling,
we
report
monotonic
log-linear
reduction
mean-squared
error
(MSE)
amount
data.
model
find
MSE
to
be
nonlinear
size
ANN
Furthermore,
observe
dataset
are
influenced
particular
choice
architecture
but
not
precise
experimental
source
Our
results
fall
short
producing
long-horizon
predictive
generative
suggest
directions
achieve
those.
In
our
extrapolate
recording
more
is
fruitful
near-term
approach
obtaining
better
system.