Different
speeds
of
locomotion
require
heterogeneous
spinal
populations,
but
a
common
mode
rhythm
generation
is
presumed
to
exist.
Here,
we
explore
the
cellular
versus
synaptic
origins
rhythmicity
at
different
by
performing
electrophysiological
recordings
from
premotor
excitatory
interneurons
in
larval
zebrafish.
Chx10-labeled
V2a
neurons
are
divided
into
least
two
morphological
subtypes
proposed
play
distinct
roles
timing
and
intensity
control.
Consistent
with
generating
output
patterning
functions
within
population,
find
that
descending
recruited
exclusively
slow
or
fast
exhibit
intrinsic
properties
suitable
for
rhythmogenesis
those
speeds,
while
bifurcating
more
reliably
all
lack
appropriate
rhythmogenic
properties.
Unexpectedly,
however,
phasic
firing
patterns
during
non-rhythmogenic
alike
best
explained
modes
inhibition
linked
cell-type
speed.
At
reciprocal
supports
firing,
recurrent
helps
pattern
motor
output.
In
contrast,
rely
on
alone
Our
findings
suggest
cell-type-specific,
not
common,
generate
coordinate
locomotion.
Nature Neuroscience,
Год журнала:
2023,
Номер
27(1), С. 78 - 89
Опубликована: Ноя. 2, 2023
Abstract
The
flexibility
of
motor
actions
is
ingrained
in
the
diversity
neurons
and
how
they
are
organized
into
functional
circuit
modules,
yet
our
knowledge
molecular
underpinning
modularity
remains
limited.
Here
we
use
adult
zebrafish
to
link
motoneurons
(MNs)
rhythm-generating
V2a
interneurons
(INs)
with
modular
organization
that
responsible
for
changes
locomotor
speed.
We
show
MNs
INs
reflects
their
segregation
slow,
intermediate
or
fast
subtypes.
Furthermore,
reveal
shared
signatures
between
three
speed
modules.
Overall,
by
characterizing
relates
function,
connectivity
behavior,
study
provides
important
insights
not
only
mechanisms
neuronal
but
also
charting
circuits
general.
Current Opinion in Genetics & Development,
Год журнала:
2024,
Номер
86, С. 102179 - 102179
Опубликована: Март 14, 2024
The
chronologically
ordered
generation
of
distinct
cell
types
is
essential
for
the
establishment
neuronal
diversity
and
formation
circuits.
Recently,
single-cell
transcriptomic
analyses
various
areas
developing
vertebrate
nervous
system
have
provided
evidence
existence
a
shared
temporal
patterning
program
that
partitions
neurons
based
on
timing
neurogenesis.
In
this
review,
I
summarize
findings
lead
to
proposal
before
focusing
spinal
cord
discuss
how
in
general
specifically
contributes
Abstract
Musculoskeletal
(MSK)
disorders
significantly
burden
patients
and
society,
resulting
in
high
healthcare
costs
productivity
loss.
These
are
the
leading
cause
of
physical
disability,
their
prevalence
is
expected
to
increase
as
sedentary
lifestyles
become
common
global
population
elderly
increases.
Proper
innervation
critical
maintaining
MSK
function,
nerve
damage
or
dysfunction
underlies
various
disorders,
underscoring
potential
restoring
function
disorder
treatment.
However,
most
tissue
engineering
strategies
have
overlooked
significance
innervation.
This
review
first
expounds
upon
system
its
importance
homeostasis
functions.
will
be
followed
by
for
tissues
that
induce
post‐implantation
situ
pre‐innervated.
Subsequently,
research
progress
modeling
using
innervated
organoids
organs‐on‐chips
(OoCs)
analyzed.
Finally,
future
development
treat
recapitulate
disease
mechanisms
discussed.
provides
valuable
insights
into
underlying
principles,
methods,
applications
tissues,
paving
way
targeted,
efficacious
therapies
conditions.
Journal of Neuroscience,
Год журнала:
2024,
Номер
44(30), С. e2315232024 - e2315232024
Опубликована: Май 22, 2024
Mature
vertebrates
maintain
posture
using
vestibulospinal
neurons
that
transform
sensed
instability
into
reflexive
commands
to
spinal
motor
circuits.
Postural
stability
improves
across
development.
However,
due
the
complexity
of
terrestrial
locomotion,
contributions
postural
refinement
in
early
life
remain
unexplored.
Here
we
leveraged
relative
simplicity
underwater
locomotion
quantify
consequences
losing
during
development
larval
zebrafish
undifferentiated
sex.
By
comparing
at
two
timepoints,
discovered
later
lesions
led
greater
instability.
Analysis
thousands
individual
swim
bouts
revealed
disrupted
movement
timing
and
corrective
reflexes
without
impacting
kinematics,
this
effect
was
particularly
strong
older
larvae.
Using
a
generative
model
swimming,
showed
how
these
disruptions
could
account
for
increased
variability
both
timepoints.
Finally,
late
fin/trunk
coordination
observed
larvae,
linking
control
schemes
used
navigate
depth.
Since
were
considerably
more
disruptive
stability,
conclude
balance
increase
as
larvae
mature.
Vestibulospinal
are
highly
conserved
vertebrates;
therefore
propose
they
substrate
developmental
improvements
control.
Science,
Год журнала:
2025,
Номер
387(6729), С. 85 - 90
Опубликована: Янв. 2, 2025
Vertebrates
stabilize
gaze
using
a
neural
circuit
that
transforms
sensed
instability
into
compensatory
counterrotation
of
the
eyes.
Sensory
feedback
tunes
this
vestibulo-ocular
reflex
throughout
life.
We
studied
functional
development
components
in
larval
zebrafish,
with
and
without
sensation.
Blind
fish
normally,
responses
to
body
tilts
mature
before
behavior.
In
contrast,
synapses
between
motor
neurons
eye
muscles
time
course
similar
behavioral
maturation.
Larvae
vestibular
sensory
experience,
but
neuromuscular
junctions,
had
strong
reflex.
Development
junction,
not
therefore
determines
rate
maturation
an
ancient
Cerebellar
dysfunction
leads
to
postural
instability.
Recent
work
in
freely
moving
rodents
has
transformed
investigations
of
cerebellar
contributions
posture.
However,
the
combined
complexity
terrestrial
locomotion
and
rodent
cerebellum
motivate
new
approaches
perturb
function
simpler
vertebrates.
Here,
we
adapted
a
validated
chemogenetic
tool
(TRPV1/capsaicin)
describe
role
Purkinje
cells
—
output
neurons
cortex
as
larval
zebrafish
swam
depth.
We
achieved
both
bidirectional
control
(activation
ablation)
while
performing
quantitative
high-throughput
assessment
posture
locomotion.
Activation
modified
pitch
(nose-up/nose-down)
axis.
Similarly,
ablations
disrupted
pitch-axis
fin-body
coordination
responsible
for
climbs.
Postural
disruption
was
more
widespread
older
larvae,
offering
window
into
emergent
roles
developing
Finally,
found
that
activity
could
individually
collectively
encode
tilt
direction,
key
feature
neurons.
Our
findings
delineate
an
expected
vestibular
sensation
zebrafish,
establishing
validity
TRPV1/capsaicin-mediated
perturbations
simple,
genetically-tractable
vertebrate.
Moreover,
by
comparing
cell
time,
uncover
signatures
emerging
across
early
development.
This
takes
major
step
towards
understanding
ancestral
regulating
maturation.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 6, 2025
Information
flow
through
circuits
is
dictated
by
the
precise
connectivity
of
neurons
and
glia.
While
a
single
astrocyte
can
contact
many
synapses,
how
glial-synaptic
interactions
are
arranged
within
circuit
to
impact
information
remains
understudied.
Here,
we
use
local
spinal
sensorimotor
in
zebrafish
as
model
understand
astroglia
connected
vertebrate
circuit.
With
semi-automated
cellular
reconstructions
automated
approaches
map
all
synaptic
connections,
identified
connections
circuit,
from
dorsal
root
ganglia
interneurons
finally
motor
neurons.
This
revealed
complex
network
that
interact
We
then
mapped
glial
processes
tripartite
synapses
demonstrate
equally
distributed
across
supporting
idea
glia
modulate
at
different
levels.
show
multiple
astroglia,
including
bona
fide
astrocytes,
sensory
neuron's
each
these
parts
detailed
reveals
an
extensive
process
stimuli
vertebrate.
utilized
this
ultrastructural
thresholding
modulation
could
alter
circuits.
validated
with
GCaMP6s
imaging
ganglia,
astroglia.
work
provides
foundational
resource
detailing
organization
offering
insights
influence
neural
networks.
Cerebellar
dysfunction
leads
to
postural
instability.
Recent
work
in
freely
moving
rodents
has
transformed
investigations
of
cerebellar
contributions
posture.
However,
the
combined
complexity
terrestrial
locomotion
and
rodent
cerebellum
motivate
new
approaches
perturb
function
simpler
vertebrates.
Here,
we
adapted
a
validated
chemogenetic
tool
(TRPV1/capsaicin)
describe
role
Purkinje
cells
—
output
neurons
cortex
as
larval
zebrafish
swam
depth.
We
achieved
both
bidirectional
control
(activation
ablation)
while
performing
quantitative
high-throughput
assessment
posture
locomotion.
Activation
modified
pitch
(nose-up/nose-down)
axis.
Similarly,
ablations
disrupted
pitch-axis
fin-body
coordination
responsible
for
climbs.
Postural
disruption
was
more
widespread
older
larvae,
offering
window
into
emergent
roles
developing
Finally,
found
that
activity
could
individually
collectively
encode
tilt
direction,
key
feature
neurons.
Our
findings
delineate
an
expected
vestibular
sensation
zebrafish,
establishing
validity
TRPV1/capsaicin-mediated
perturbations
simple,
genetically
tractable
vertebrate.
Moreover,
by
comparing
cell
time,
uncover
signatures
emerging
across
early
development.
This
takes
major
step
towards
understanding
ancestral
regulating
maturation.
Different
speeds
of
locomotion
require
heterogeneous
spinal
populations,
but
a
common
mode
rhythm
generation
is
presumed
to
exist.
Here,
we
explore
the
cellular
versus
synaptic
origins
rhythmicity
at
different
by
performing
electrophysiological
recordings
from
premotor
excitatory
interneurons
in
larval
zebrafish.
Chx10-labeled
V2a
neurons
are
divided
into
least
two
morphological
subtypes
proposed
play
distinct
roles
timing
and
intensity
control.
Consistent
with
generating
output
patterning
functions
within
population,
find
that
descending
recruited
exclusively
slow
or
fast
exhibit
intrinsic
properties
suitable
for
rhythmogenesis
those
speeds,
while
bifurcating
more
reliably
all
lack
appropriate
rhythmogenic
properties.
Unexpectedly,
however,
phasic
firing
patterns
during
non-rhythmogenic
alike
best
explained
modes
inhibition
linked
cell
type
speed.
At
reciprocal
supports
firing,
recurrent
helps
pattern
motor
output.
In
contrast,
rely
on
alone
Our
findings
suggest
cell-type-specific,
not
common,
generate
coordinate
locomotion.