The Journal of Physiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 20, 2024
Abstract
Previous
studies
established
strong
links
between
morphological
characteristics
of
mammalian
hindlimb
muscles
and
their
sensorimotor
functions
during
locomotion.
Less
is
known
about
the
role
forelimb
morphology
in
motor
outputs
generation
sensory
signals.
Here,
we
measured
46
from
six
cats.
These
included
muscle
attachments,
physiological
cross‐sectional
area
(PCSA)
fascicle
length.
We
also
recorded
full‐body
mechanics
EMG
activity
level
overground
treadmill
locomotion
seven
16
adult
cats
either
sex,
respectively.
computed
forces
along
with
force‐
length‐dependent
signals
mapped
onto
corresponding
cervical
spinal
segments.
found
that
patterns
afferent
activities
were
strongly
affected
by
muscle's
moment
arm,
PCSA
Morphology
shoulder
suggests
distinct
roles
forelimbs
lateral
force
production
movements.
Patterns
long
fibres
(brachioradialis,
extensor
carpi
radialis)
closely
matched
overall
length,
whereas
pattern
biceps
brachii
length
afferents
orientation.
conclude
cat
contributes
substantially
to
locomotor
function,
particularly
control
stability
turning,
rather
than
propulsion.
image
Key
points
Little
producing
generating
somatosensory
This
information
needed
understand
contributions
control.
forelimbs,
walking
electromyographic
activity,
arms,
velocity,
activation,
muscles,
as
well
length‐
force‐dependent
walking.
demonstrated
contribute
proprioceptive
regulation
cycle
phase
transitions
stability.
The
obtained
can
guide
development
biologically
accurate
neuromechanical
models
quadrupedal
for
exploring
testing
novel
methods
treatments
central
nervous
system
pathologies
modulating
neural
pathways
controlling
forelimbs/arms.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 17, 2024
Abstract
Animals
change
their
location
in
space
by
means
of
walking,
running,
swimming,
or
flying,
a
series
rhythmic
motor
behaviours
that
together
are
defined
as
locomotion.
Individual
types
locomotion
require
unique
coordinated
pattern
muscle
contractions
can
be
inferred
the
joints
across
body.
Implementations
recent
advancements
machine
learning
(ML),
such
DeepLabCut
and
Simi
Shape,
have
automated
tracking
body
posture,
even
markerless
subjects.
Despite
ML
algorithms
alleviating
effort,
making
sense
tracked
points
still
requires
substantial
amounts
manual
labour
lacks
standardisation
research
labs.
To
this
end,
we
developed
AutoGaitA
(Automated
Gait
Analysis),
an
open-source
Python
toolbox
designed
to
automate
analysis
normalising
step
cycle,
extracting
meaningful
features
from
coordinates
(e.g.
angles,
velocity,
acceleration)
allowing
intra-
inter-animal
comparisons.
Here,
employed
proof
principles
experiments
show
age-dependent
changes
flies,
mice
humans,
adaptation
mechanisms
mice,
compare
key
walking
species.
’s
adaptability
any
kind
behaviour
species
interest
makes
it
valuable
tool
for
community
standardise
genotypes,
disease
states
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 15, 2025
Summary
The
dorsal
horn
of
the
mammalian
spinal
cord
is
an
exquisite
example
form
serving
function.
It
comprised
diverse
neuronal
populations
stacked
into
laminae,
each
which
receives
different
circuit
connections
and
plays
specialized
roles
in
behavior.
An
outstanding
question
how
this
organization
emerges
during
development
from
apparently
homogeneous
pool
neural
progenitors.
Here,
we
found
that
neurons
are
diversified
by
time,
with
families
related
cell
types
born
as
temporal
cohorts,
a
spatial-molecular
gradient
specifies
full
array
individual
types.
Excitatory
then
settle
chronotopic
arrangement
transforms
their
progressive
birthdates
anatomical
order.
This
establishes
these
also
required
for
spatial
inhibitory
sensory
axons.
work
reveals
essential
ontogenetic
principles
shape
progenitors
architecture
subserve
sensorimotor
Highlights
-
Temporal
cohorts
late-born
give
rise
to
Sequentially-born
excitatory
neuron
adjacent
laminae
Laminar
structure
specifically
requires
(but
not
or
sensory)
Graded
expression
Zic
transcription
factors
directs
fine
identity
Proceedings of the National Academy of Sciences,
Год журнала:
2025,
Номер
122(15)
Опубликована: Апрель 8, 2025
Various
strategies
targeting
spinal
locomotor
circuitry
have
been
associated
with
functional
improvements
after
cord
injury
(SCI).
However,
the
neuronal
populations
mediating
beneficial
effects
remain
largely
unknown.
Using
a
combination
therapy
in
mouse
model
of
complete
SCI,
we
show
that
virally
delivered
brain-derived
neurotrophic
factor
(BDNF)
(AAV-BDNF)
activates
hindlimb
stepping
and
causes
hyperreflexia,
whereas
submotor
threshold
epidural
stimulation
(ES)
reduces
BDNF-induced
hyperreflexia.
Given
their
role
gating
proprioceptive
afferents
as
potential
convergence
point
BDNF
ES,
hypothesized
an
enhanced
excitability
inhibitory
RORβ
neurons
would
be
improvements.
Ex
vivo
slice
recordings
from
mice
range
hyperreflexia
scores
revealed
was
related
to
outcome
post-SCI.
Mice
poor
function
SCI
had
less
excitable
neurons,
but
similar
between
uninjured
“best
stepping”
groups.
Further,
chemogenetic
activation
reduced
improved
stepping,
ES.
Our
findings
identify
target
population
limit
enhance
SCI.
Cells,
Год журнала:
2024,
Номер
13(8), С. 652 - 652
Опубликована: Апрель 9, 2024
The
differential
expression
of
transcription
factors
during
embryonic
development
has
been
selected
as
the
main
feature
to
define
specific
subclasses
spinal
interneurons.
However,
recent
studies
based
on
single-cell
RNA
sequencing
and
transcriptomic
experiments
suggest
that
this
approach
might
not
be
appropriate
in
adult
cord,
where
interneurons
show
overlapping
profiles,
especially
ventral
region.
This
constitutes
a
major
challenge
for
identification
direct
targeting
populations
could
involved
locomotor
recovery
after
traumatic
cord
injury
adults.
Current
experimental
therapies,
including
electrical
stimulation,
training,
pharmacological
treatments,
or
cell
implantation,
have
resulted
improvements
behavior
rely
modulation
activity
connectivity
located
surroundings
lesion
core
formation
detour
circuits.
very
few
publications
clarify
identity
these
cells.
In
work,
we
review
premotor
were
able
create
new
intraspinal
circuits
different
kinds
injury,
highlighting
difficulties
encountered
by
researchers,
classify
populations.
Journal of Neuroscience,
Год журнала:
2024,
Номер
44(40), С. e1238242024 - e1238242024
Опубликована: Окт. 2, 2024
Motor
circuits
represent
the
main
output
of
central
nervous
system
and
produce
dynamic
behaviors
ranging
from
relatively
simple
rhythmic
activities
like
swimming
in
fish
breathing
mammals
to
highly
sophisticated
dexterous
movements
humans.
Despite
decades
research,
development
function
motor
remain
poorly
understood.
Breakthroughs
field
recently
provided
new
tools
tractable
model
systems
that
set
stage
discover
molecular
mechanisms
circuit
logic
underlying
control.
Here,
we
describe
recent
advances
both
vertebrate
(mouse,
frog)
invertebrate
(nematode,
fruit
fly)
on
cellular
enable
develop
highlight
conserved
divergent
necessary
for
development.
Frontiers in Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Июль 18, 2024
Amyotrophic
lateral
sclerosis
(ALS)
consists
of
a
group
adult-onset
fatal
and
incurable
neurodegenerative
disorders
characterized
by
the
progressive
death
motor
neurons
(MNs)
throughout
central
nervous
system
(CNS).
At
first,
ALS
was
considered
to
be
an
MN
disease,
caused
cell-autonomous
mechanisms
acting
specifically
in
MNs.
Accordingly,
data
from
patients
animal
models
revealed
alterations
excitability
multiple
neuronal
populations,
including
MNs,
which
were
associated
with
variety
cellular
perturbations
such
as
protein
aggregation,
ribonucleic
acid
(RNA)
metabolism
defects,
calcium
dyshomeostasis,
modified
electrophysiological
properties,
autophagy
malfunctions.
However,
experimental
evidence
rapidly
demonstrated
involvement
other
types
cells,
glial
etiopathogenesis
through
non-cell
autonomous
mechanisms.
Surprisingly,
contribution
pre-motor
interneurons
(INs),
regulate
activity
could
therefore
critically
modulate
their
at
onset
or
during
progression
has
date
been
severely
underestimated.
In
this
article,
we
review
detail
how
spinal
INs
are
affected
possible
disease.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 26, 2024
Locomotor
behaviors
are
performed
by
organisms
throughout
life,
despite
developmental
changes
in
cellular
properties,
neural
connectivity,
and
biomechanics.
The
basic
rhythmic
activity
the
central
nervous
system
that
underlies
locomotion
is
thought
to
be
generated
via
a
complex
balance
between
network
intrinsic
properties.
Within
mature
mammalian
spinal
locomotor
circuitry,
we
have
yet
determine
which
properties
of
interneurons
(INs)
critical
rhythmogenesis
how
they
change
during
development.
Here,
combined
whole
cell
patch
clamp
recordings,
immunohistochemistry,
RNAscope
targeting
lumbar
Shox2
INs
mice,
known
involved
rhythm
generation.
We
focused
on
putatively
rhythmogenic
ionic
currents
expression
corresponding
ion
channels
across
postnatal
time
points
mice.
show
subsets
display
voltage-sensitive
conductances,
addition
respective
channels,
may
contribute
or
shape
bursting.
Persistent
inward
currents,
M-type
potassium
slow
afterhyperpolarization,
T-type
calcium
enhanced
with
age.
In
contrast,
hyperpolarization-activated
A-type
were
either
found
low
prevalence
neonatal,
juvenile,
adult
did
not
developmentally
change.
become
more
electrophysiologically
diverse
juvenile
ages,
when
behavior
weight-bearing.
These
results
suggest
shift
magnitude
important
for
mature,
weight-bearing
behavior.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 5, 2024
SUMMARY
Various
strategies
targeting
spinal
locomotor
circuitry
have
been
associated
with
functional
improvements
after
cord
injury
(SCI).
However,
the
neuronal
populations
mediating
beneficial
effects
remain
largely
unknown.
In
a
mouse
model
of
complete
SCI,
virally-delivered
BDNF
(AAV-BDNF)
activates
hindlimb
stepping
and
causes
hyperreflexia,
whereas
sub-motor
threshold
epidural
stimulation
(ES)
reduced
BDNF-induced
hyperreflexia.
Given
their
role
in
gating
proprioceptive
afferents
potential
convergence
point
ES,
we
hypothesized
that
an
enhanced
excitability
inhibitory
RORβ
neurons
would
be
improvements.
Ex
vivo
slice
recordings
revealed
was
decreased
mice
poor
function
but
similar
between
uninjured
‘best
stepping’
SCI
groups.
Further,
chemogenetic
excitation
hyperreflexia
improved
stepping,
to
ES.
Our
findings
identify
as
target
population
limit
enhance
SCI.
The
differential
expression
of
transcription
factors
during
embryonic
development
has
been
selected
as
the
main
feature
to
define
specific
subclasses
spinal
interneurons.
However,
recent
studies
based
on
single-cell
RNA
sequencing
and
transcriptomic
experiments
suggest
that
this
approach
could
not
be
appropriate
in
adult
cord,
where
interneurons
show
overlapping
profiles,
especially
ventral
region.
This
constitutes
a
major
challenge
for
identification
direct
targeting
populations
involved
locomotor
recovery
after
traumatic
cord
injury
adults.
Current
experimental
therapies
including
electrical
stimulation,
training,
pharmacological
treatments,
or
cell
implantation
resulted
improvements
behaviour,
rely
modulation
activity
connectivity
located
surroundings
lesion
core
formation
detour
circuits.
very
few
publications
clarify
identity
these
cells.
In
work,
we
review
premotor
were
able
create
new
intraspinal
circuits
different
kinds
injury,
highlighting
difficulties
encountered
by
researchers
classify
populations.
Previous
studies
established
strong
links
between
morphological
characteristics
of
mammalian
hindlimb
muscles
and
their
sensorimotor
functions
during
locomotion.
Less
is
known
about
the
role
forelimb
morphology
in
motor
outputs
generation
sensory
signals.
Here,
we
measured
46
from
6
cats.
These
included
muscle
attachments,
physiological
cross-sectional
area
(PCSA),
fascicle
length,
etc.
We
also
recorded
full-body
mechanics
EMG
activity
level
overground
treadmill
locomotion
7
16
adult
cats
either
sex,
respectively.
computed
forces
along
with
force-
length-dependent
signals
mapped
onto
corresponding
cervical
spinal
segments.
found
that
patterns
afferent
activities
were
strongly
affected
by
muscle's
moment
arm,
PCSA,
length.
Morphology
shoulder
suggests
distinct
roles
forelimbs
lateral
force
production
movements.
Patterns
long
fibers
(brachioradialis,
extensor
carpi
radialis)
closely
matched
overall
whereas
pattern
biceps
brachii
orientation.
conclude
cat
contributes
substantially
to
locomotor
function,
particularly
control
stability
turning,
rather
than
propulsion.