Differential modification of ascending spinal outputs in acute and chronic pain states
Neuron,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 1, 2025
Pain
hypersensitivity
arises
from
the
induction
of
plasticity
in
peripheral
and
spinal
somatosensory
neurons,
which
modifies
nociceptive
input
to
brain,
altering
pain
perception.
We
applied
longitudinal
calcium
imaging
dorsal
projection
neurons
determine
whether
how
representation
stimuli
anterolateral
tract,
principal
pathway
transmitting
signals
changes
between
distinct
states.
In
healthy
mice,
we
identified
stable
outputs
selective
for
cooling
or
warming
a
neuronal
ensemble
activated
by
noxious
thermal
mechanical
stimuli.
Induction
acute
sensitization
topical
capsaicin
transiently
re-tuned
output
encode
low-intensity
contrast,
nerve
injury
resulted
persistent
suppression
innocuous
coupled
with
activation
normally
silent
population
high-threshold
neurons.
These
results
demonstrate
differential
modulation
brain
during
neuropathic
Язык: Английский
Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(23)
Опубликована: Май 28, 2024
The
anterolateral
system
(ALS)
is
a
major
ascending
pathway
from
the
spinal
cord
that
projects
to
multiple
brain
areas
and
underlies
perception
of
pain,
itch,
skin
temperature.
Despite
its
importance,
our
understanding
this
has
been
hampered
by
considerable
functional
molecular
diversity
constituent
cells.
Here,
we
use
fluorescence-activated
cell
sorting
isolate
ALS
neurons
belonging
Phox2a-lineage
for
single-nucleus
RNA
sequencing.
We
reveal
five
distinct
clusters
(ALS1-5)
document
their
laminar
distribution
in
using
situ
hybridization.
identify
three
located
predominantly
laminae
I–III
dorsal
horn
(ALS1-3)
two
with
bodies
deeper
(ALS4
ALS5).
Our
findings
transcriptional
logic
neuronal
adult
mouse
uncover
identity
previously
identified
classes
projection
neurons.
also
show
these
signatures
can
be
used
target
groups
retrograde
viral
tracing.
Overall,
provide
valuable
resource
studying
somatosensory
biology
targeting
subclasses
Язык: Английский
VLK drives extracellular phosphorylation of EphB2 to govern the EphB2-NMDAR interaction and injury-induced pain
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 18, 2024
Abstract
Phosphorylation
of
hundreds
protein
extracellular
domains
is
mediated
by
two
kinase
families,
yet
the
significance
these
kinases
underexplored.
Here,
we
find
that
presynaptic
release
tyrosine
directed-ectokinase,
Vertebrate
Lonesome
Kinase
(VLK/Pkdcc),
necessary
and
sufficient
for
direct
interaction
between
EphB2
GluN1
at
synapses,
phosphorylation
ectodomain
EphB2,
injury-induced
pain.
Pkdcc
an
essential
gene
in
nervous
system,
VLK
found
synaptic
vesicles,
released
from
neurons
a
SNARE-dependent
fashion.
expressed
nociceptive
sensory
where
neuron-specific
knockout
renders
mice
impervious
to
post-surgical
pain,
without
changing
proprioception.
defines
mechanism
regulates
protein-protein
non-opioid-dependent
pain
response
injury.
One-Sentence
Summary
Synaptic
interactions
are
regulated
spinal
cord.
Язык: Английский
A Viral Labelling Study of Spinal Trigeminal Nucleus Caudalis Projection Neurons Targeting the Parabrachial Nucleus
Journal of Neurochemistry,
Год журнала:
2025,
Номер
169(3)
Опубликована: Март 1, 2025
Projection
neurons
(PNs)
in
the
Spinal
Trigeminal
Nucleus
Caudalis
(Sp5C)
relay
orofacial
nociceptive
information
to
higher
brain
regions
such
as
thalamus
and
parabrachial
nucleus
(PBN).
Our
understanding
of
Sp5C
PN
organisation
function
has
advanced
less
than
parallel
spinal
cord
output
system
despite
their
corresponding
roles
for
transmission
signals
from
region
body
respectively.
Viral
vectors
are
an
established
approach
studying
circuit
connectivity
nervous
system,
but
different
serotypes
known
produce
variable
results
across
circuits.
As
such,
we
sought
validate
utility
two
common
viral
research:
retrograde
adeno-associated
virus
serotype
2
(rgAAV)
9
(AAV9),
identifying
analysing
PNs
that
project
PBN.
Following
unilateral
injections
either
into
PBN,
many
projection
were
retrogradely
labelled.
For
both
serotypes,
these
labelled
bilaterally
with
a
strong
bias
ipsilateral
Sp5C.
Within
Sp5C,
similar
levels
labelling
present
superficial
deep
regions,
contrasting
previous
work
showed
greater
by
AAV9
versus
rgAAV.
Comparisons
age
dependence
when
made
young
adult
animals.
Finally,
demonstrate
successful
Cre-dependent
recombination
selectively
express
channelrhodopsin-2
neurons.
Together,
experiments
show
rgAAV
transduction
provide
basis
future
study
afferent
efferent
functions
population
health
disease.
Язык: Английский
Anatomical characterisation of somatostatin-expressing neurons belonging to the anterolateral system
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Март 20, 2025
Abstract
Anterolateral
system
(ALS)
spinal
projection
neurons
are
essential
for
pain
perception.
However,
these
cells
heterogeneous,
and
there
has
been
extensive
debate
about
the
roles
of
ALS
populations
in
different
dimensions.
We
recently
performed
single-nucleus
RNA
sequencing
on
a
developmentally-defined
subset
neurons,
identified
5
transcriptomic
populations.
One
these,
ALS4,
consists
that
express
Sst
,
gene
coding
somatostatin,
we
reported
were
located
lateral
part
lamina
V.
Here
use
Cre
mouse
line
to
characterise
define
their
axonal
projections.
find
axons
ascend
mainly
ipsilateral
side,
giving
off
collaterals
throughout
course
cord.
They
target
various
brainstem
nuclei,
including
parabrachial
internal
nucleus,
posterior
triangular
medial
dorsal
thalamic
nuclei.
also
show
L4
segment
is
expressed
by
~
75%
V
around
120
-positive
each
side.
Our
findings
indicate
this
relatively
large
population,
based
targets
conclude
they
likely
contribute
affective-motivational
dimension
pain.
Язык: Английский
An electrophysiologist’s guide to dorsal horn excitability and pain
Frontiers in Cellular Neuroscience,
Год журнала:
2025,
Номер
19
Опубликована: Апрель 2, 2025
The
dorsal
horn
of
the
spinal
cord
represents
first
site
in
central
nervous
system
(CNS)
where
nociceptive
signals
are
integrated.
As
a
result,
there
has
been
rapid
growth
number
studies
investigating
ionic
mechanisms
regulating
excitability
neurons
under
normal
and
pathological
conditions.
We
believe
that
it
is
time
to
look
back
critically
examine
what
picture
emerges
from
this
wealth
studies.
What
actual
types
described
literature
based
on
electrophysiological
criteria?
Are
these
electrophysiologically-defined
subpopulations
strongly
linked
specific
morphological,
functional,
or
molecular
traits?
properties
stable,
can
they
change
during
development
response
peripheral
injury?
Here
we
provide
an
in-depth
overview
both
early
recent
publications
explore
factors
influencing
neuronal
(including
intrinsic
membrane
synaptic
transmission),
how
vary
across
distinct
subtypes
neurons,
such
altered
by
nerve
tissue
damage.
meta-research
presented
below
leads
conclusion
comprised
highly
heterogeneous
which
observed
given
neuron
often
fail
easily
predict
other
as
biochemical
phenotype
morphology.
This
highlights
need
for
future
more
fully
interrogate
multi-modal
manner.
Язык: Английский
Lateral lamina V projection neuron axon collaterals connect sensory processing across the dorsal horn of the mouse spinal cord
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Ноя. 1, 2024
Spinal
projection
neurons
(PNs)
are
defined
by
long
axons
that
travel
from
their
origin
in
the
spinal
cord
to
brain
where
they
relay
sensory
information
body.
The
existence
and
function
of
a
substantial
axon
collateral
network,
also
arising
PNs
remaining
within
cord,
is
less
well
appreciated.
Here
we
use
retrograde
viral
transduction
strategy
characterise
novel
subpopulation
deep
dorsal
horn
spinoparabrachial
neurons.
Brainbow
assisted
analysis
confirmed
virally
labelled
PN
cell
bodies
formed
discrete
column
lateral
part
Lamina
V
(LV
Язык: Английский