Movement
is
a
key
feature
of
animal
systems,
yet
its
embryonic
origins
are
not
fully
understood.
Here,
we
investigate
the
genetic
basis
underlying
onset
movement
in
Drosophila
focusing
on
role
played
by
small
non-coding
RNAs
(microRNAs,
miRNAs).
To
this
end,
first
develop
quantitative
behavioural
pipeline
capable
tracking
large
populations
fly
embryos,
and
using
system,
discover
that
miRNA
miR-2b-1
plays
emergence
movement.
Through
combination
spectral
analysis
motor
patterns,
cell
sorting
RNA
situs,
reconstitution
tests,
neural
optical
imaging
define
influences
exerting
actions
developing
nervous
system.
Furthermore,
through
bioinformatics
coupled
to
manipulation
expression
phenocopy
tests
identify
previously
uncharacterised
(but
evolutionarily
conserved)
chloride
channel
encoding
gene
–
which
term
Mo
vement
Modula
tor
(
Motor
)
as
target
mechanistically
links
Cell-specific
null
mutant
background,
followed
assays
analyses,
suggest
affects
effects
sensory
elements
circuitry,
rather
than
domain.
Our
work
thus
reports
system
regulating
movement,
suggesting
other
miRNAs
likely
play
developmental
process
well
species.
Developing
neural
circuits
are
influenced
by
activity
and
especially
sensitive
to
changes
in
during
critical
periods
(CPs)
of
development.
Changes
occurring
a
CP
often
become
‘locked
in’
so
that
they
affect
the
mature
network.
Indeed,
several
neurodevelopmental
disorders
have
been
linked
excessive
such
periods.
It
is,
therefore,
important
identify
those
aspects
circuit
development
CP.
In
this
study,
we
take
advantage
genetic
tractability
Drosophila
show
perturbation
an
embryonic
permanently
alters
properties
locomotor
circuit.
Specific
include
increased
synchronicity
motoneuron
greater
strengthening
excitatory
over
inhibitory
synaptic
drive
motoneurons.
These
sufficient
reduce
network
robustness,
evidenced
sensitivity
induced
seizure.
We
also
can
rescue
these
when
is
mitigated
inhibition
provided
mechanosensory
neurons.
Similarly,
demonstrate
dose-dependent
relationship
between
experienced
extent
which
it
possible
hyperexcitable
phenotype
characteristic
para
bss
mutation.
This
suggests
developing
must
be
exposed
properly
balanced
sum
excitation
achieve
normal
function.
Our
results,
provide
novel
insight
into
how
shapes
specific
elements
circuit,
period
integrated
tune
environment
will
likely
Frontiers in Neuroscience,
Год журнала:
2025,
Номер
19
Опубликована: Март 20, 2025
We
investigated
developmental
changes
in
neuromotor
activity
patterns
Drosophila
melanogaster
larvae
by
combining
calcium
imaging
with
a
novel
graph-based
mathematical
framework.
This
allows
to
perform
relevant
quantitative
comparisons
between
first
(L1)
and
early
third
(L3)
instar
larvae.
found
that
L1
exhibit
higher
frequencies
of
spontaneous
neural
fail
propagate,
indicating
less
mature
system.
In
contrast,
L3
show
efficient
initiation
propagation
along
the
entire
ventral
nerve
cord
(VNC),
resulting
longer
chains.
The
time
chain
VNC
is
shorter
than
L3,
probably
reflecting
increased
length
VNC.
On
other
hand,
peristaltic
waves
through
whole
body
during
locomotion
much
faster
L1,
so
correlating
velocities
greater
dispersal
rates.
Hence,
VNC-body
interaction
determines
characteristics
crawling
Further,
asymmetrical
neuronal
activity,
predominantly
anterior
segments
larvae,
was
associated
turning
behaviors
enhanced
navigation.
These
findings
illustrate
proposed
model
provides
systematic
method
analyze
across
stages,
for
instance,
helping
uncover
maturation
stages
circuits
their
role
locomotion.
Developing
neural
circuits
are
influenced
by
activity
and
especially
sensitive
to
changes
in
during
critical
periods
(CPs)
of
development.
Changes
occurring
a
CP
often
become
'locked
in'
so
that
they
affect
the
mature
network.
Indeed,
several
neurodevelopmental
disorders
have
been
linked
excessive
such
periods.
It
is,
therefore,
important
identify
those
aspects
circuit
development
CP.
In
this
study,
we
take
advantage
genetic
tractability
Drosophila
show
perturbation
an
embryonic
permanently
alters
properties
locomotor
circuit.
Specific
include
increased
synchronicity
motoneuron
greater
strengthening
excitatory
over
inhibitory
synaptic
drive
motoneurons.
These
sufficient
reduce
network
robustness,
evidenced
sensitivity
induced
seizure.
We
also
can
rescue
these
when
is
mitigated
inhibition
provided
mechanosensory
neurons.
Similarly,
demonstrate
dose-dependent
relationship
between
experienced
extent
which
it
possible
hyperexcitable
phenotype
characteristic
parabss
mutation.
This
suggests
developing
must
be
exposed
properly
balanced
sum
excitation
achieve
normal
function.
Our
results,
provide
novel
insight
into
how
shapes
specific
elements
circuit,
period
integrated
tune
environment
will
likely
Frontiers in Physiology,
Год журнала:
2022,
Номер
13
Опубликована: Дек. 2, 2022
Critical
periods
are
phases
of
heightened
plasticity
that
occur
during
the
development
neural
networks.
Beginning
with
pioneering
work
Hubel
and
Wiesel,
which
identified
a
critical
period
for
formation
ocular
dominance
in
mammalian
visual
network
connectivity,
have
been
many
circuits,
both
sensory
motor,
across
phyla,
suggesting
universal
phenomenon.
However,
key
unanswered
question
remains
why
these
forms
restricted
to
specific
developmental
rather
than
being
continuously
present.
The
consequence
this
temporal
restriction
is
activity
perturbations
can
lasting
significant
functional
consequences
mature
From
perspective,
might
enable
reproducibly
robust
function
emerge
from
ensembles
cells,
whose
properties
necessarily
variable
fluctuating.
also
offer
clinical
opportunity.
Imposed
perturbation
has
shown
remarkable
beneficial
outcomes
range
animal
models
neurological
disease
including
epilepsy.
In
review,
we
spotlight
recent
identification
locomotor
Drosophila
larva
describe
how
studying
model
organism,
because
its
simplified
nervous
system
an
almost
complete
wired
connectome,
offers
attractive
prospect
understanding
impacts
neuronal
network.
Movement
is
a
key
feature
of
animal
systems,
yet
its
embryonic
origins
are
not
fully
understood.
Here,
we
investigate
the
genetic
basis
underlying
onset
movement
in
Drosophila
focusing
on
role
played
by
small
non-coding
RNAs
(microRNAs,
miRNAs).
To
this
end,
first
develop
quantitative
behavioural
pipeline
capable
tracking
large
populations
fly
embryos,
and
using
system,
discover
that
miRNA
miR-2b-1
plays
emergence
movement.
Through
combination
spectral
analysis
motor
patterns,
cell
sorting
RNA
situs,
reconstitution
tests,
neural
optical
imaging
define
influences
exerting
actions
developing
nervous
system.
Furthermore,
through
bioinformatics
coupled
to
manipulation
expression
phenocopy
tests
identify
previously
uncharacterised
(but
evolutionarily
conserved)
chloride
channel
encoding
gene
–
which
term
Mo
vement
Modula
tor
(
Motor
)
as
target
mechanistically
links
Cell-specific
null
mutant
background,
followed
assays
analyses,
suggest
affects
effects
sensory
elements
circuitry,
rather
than
domain.
Our
work
thus
reports
system
regulating
movement,
suggesting
other
miRNAs
likely
play
developmental
process
well
species.
Journal of Neuroscience,
Год журнала:
2024,
Номер
44(19), С. e2345232024 - e2345232024
Опубликована: Апрель 8, 2024
Animals
must
distinguish
the
sensory
consequences
of
self-generated
movements
(reafference)
from
those
other-generated
(exafference).
Only
entail
production
motor
copies
(i.e.,
corollary
discharges),
which
are
compared
with
reafference
in
cerebellum
to
compute
predictive
or
internal
models
movement.
Internal
emerge
gradually
over
first
three
postnatal
weeks
rats
through
a
process
that
is
not
yet
fully
understood.
Previously,
we
demonstrated
day
(P)
8
and
P12
precerebellar
nuclei
convey
discharge
during
active
(REM)
sleep
when
pups
produce
limb
twitches.
Here,
recording
deep
cerebellar
nucleus
(interpositus,
IP)
both
sexes,
reafferent
exafferent
responses
twitches
stimulations,
respectively.
As
expected,
most
IP
units
showed
robust
However,
contrast
other
structures
throughout
brain,
relatively
few
responses.
Upon
finding
occurred
under
urethane
anesthesia,
hypothesized
inhibits
cortical
cells,
thereby
disinhibiting
IP.
In
support
this
hypothesis,
ablating
tissue
dorsal
mimicked
effects
on
exafference.
Finally,
results
suggest
twitch-related
conveyed
simultaneously
parallel
cortex
Based
these
results,
propose
provide
opportunities
for
nascent
integrate
somatotopically
organized
reafference,
enabling
development
closed-loop
circuits
and,
subsequently,
models.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 17, 2024
ABSTRACT
Understanding
how
animals
coordinate
movements
to
achieve
goals
is
a
fundamental
pursuit
in
neuroscience.
Here
we
explore
neurons
that
reside
posterior
lower-order
regions
of
locomotor
system
project
anterior
higher-order
influence
steering
and
navigation.
We
characterized
the
anatomy
functional
role
population
ascending
interneurons
ventral
nerve
cord
Drosophila
larvae.
Through
electron
microscopy
reconstructions
light
microscopy,
determined
cholinergic
19f
cells
receive
input
primarily
from
premotor
synapse
upon
diverse
array
postsynaptic
targets
within
segments
including
other
cells.
Calcium
imaging
activity
isolated
central
nervous
(CNS)
preparations
relation
motor
revealed
are
recruited
into
most
larval
programmes.
lags
behind
neuron
as
population,
encode
spatio-temporal
patterns
CNS.
Optogenetic
manipulations
cell
CNS
they
pattern
generators
underlying
exploratory
headsweeps
forward
locomotion
context
location
specific
manner.
In
behaving
animals,
activating
suppressed
slowed
locomotion,
while
inhibition
potentiated
headsweeps,
slowing
movement.
Inhibiting
ultimately
affected
ability
larvae
remain
vicinity
an
odor
source
during
olfactory
navigation
task.
Overall,
our
findings
provide
insights
monitor
shape
interactions
amongst
rhythm
complex
navigational
tasks.
Dystonia
is
a
heterogenous
movement
disorder
characterised
by
involuntary
muscle
contractions,
leading
to
abnormal
postures
and
movements.
Despite
being
the
third
most
common
disorder,
pathophysiological
mechanisms
causing
dystonia
are
incompletely
understood.
Isolated
often
caused
pathogenic
mutations
in
single
genes.
An
emerging
body
of
evidence
suggests
that
at
least
some
forms
isolated
have
strong
developmental
component,
with
effects
acting
within
discrete
periods
increased
vulnerability
during
neurodevelopment.
The
extent
which
this
feature
genetically
distinct
dystonia,
might
be
disrupted
these
periods,
remains
unclear.
During
critical
development,
neuronal
activity
instructive
maturation
circuits,
inappropriate
levels
period
can
lead
permanent
defects.
This
review,
an
intentional
focus
on
our
work,
outlines
implicating
disruptions
as
potential
mechanism
underlying
inherited
motor
disorders
general,
particular.