Cell Reports,
Год журнала:
2023,
Номер
42(4), С. 112283 - 112283
Опубликована: Март 22, 2023
Although
touch
and
itch
are
coded
by
distinct
neuronal
populations,
light
also
provokes
in
the
presence
of
exogenous
pruritogens,
resulting
a
phenomenon
called
alloknesis.
However,
cellular
molecular
mechanisms
underlying
initiation
pruritogen-induced
mechanical
sensitization
poorly
understood.
Here,
we
show
that
intradermal
injections
histamine
or
chloroquine
(CQ)
provoke
alloknesis
through
activation
TRPV1-
MrgprA3-expressing
prurioceptors,
functional
ablation
these
neurons
reverses
Moreover,
genetic
mechanosensitive
Piezo2
channel
function
from
prurioceptors
dampens
Mechanistically,
CQ
sensitize
function,
at
least
part,
phospholipase
C
(PLC)
protein
kinase
C-δ
(PKCδ)
signaling.
Collectively,
our
data
find
TRPV1+/MrgprA3+
prurioceptor-Piezo2
signaling
axis
skin.
Somatosensory
neurons
with
cell
bodies
in
the
dorsal
root
ganglia
(DRG)
project
to
skin,
muscles,
bones,
and
viscera
detect
touch
temperature
as
well
mediate
proprioception
many
types
of
interoception.
In
addition,
somatosensory
system
conveys
clinically
relevant
noxious
sensations
pain
itch.
Here,
we
used
single
nuclear
transcriptomics
characterize
transcriptomic
classes
human
DRG
that
these
diverse
stimuli.
Notably,
multiple
have
features
resemble
their
mouse
counterparts
although
expression
genes
considered
important
for
sensory
function
often
differed
between
species.
More
unexpectedly,
identified
several
no
clear
equivalent
other
This
dataset
should
serve
a
valuable
resource
community,
example
means
focusing
translational
efforts
on
molecules
conserved
across
Nature,
Год журнала:
2022,
Номер
603(7903), С. 878 - 884
Опубликована: Март 16, 2022
Abstract
Interoception,
the
ability
to
timely
and
precisely
sense
changes
inside
body,
is
critical
for
survival
1–4
.
Vagal
sensory
neurons
(VSNs)
form
an
important
body-to-brain
connection,
navigating
visceral
organs
along
rostral–caudal
axis
of
body
crossing
surface–lumen
into
appropriate
tissue
layers
5,6
The
brain
can
discriminate
numerous
signals
through
VSNs,
but
underlying
coding
strategy
remains
poorly
understood.
Here
we
show
that
VSNs
code
organ,
layer
stimulus
modality—three
key
features
interoceptive
signal—in
different
dimensions.
Large-scale
single-cell
profiling
from
seven
major
in
mice
using
multiplexed
projection
barcodes
reveals
a
‘visceral
organ’
dimension
composed
differentially
expressed
gene
modules
body’s
axis.
We
discover
another
‘tissue
layer’
with
locations
VSN
endings
organs.
Using
calcium-imaging-guided
spatial
transcriptomics,
are
organized
functional
units
similar
stimuli
across
layers;
this
constitutes
third
‘stimulus
modality’
dimension.
three
independent
feature-coding
dimensions
together
specify
many
parallel
pathways
combinatorial
manner
facilitate
complex
brainstem.
Our
study
highlights
multidimensional
architecture
mammalian
vagal
system
effective
signal
communication.
Nature,
Год журнала:
2022,
Номер
607(7918), С. 330 - 338
Опубликована: Июль 6, 2022
Abstract
Transcriptomics
has
revealed
that
cortical
inhibitory
neurons
exhibit
a
great
diversity
of
fine
molecular
subtypes
1–6
,
but
it
is
not
known
whether
these
have
correspondingly
diverse
patterns
activity
in
the
living
brain.
Here
we
show
primary
visual
cortex
(V1)
correlates
with
brain
state,
which
are
organized
by
single
factor:
position
along
main
axis
transcriptomic
variation.
We
combined
vivo
two-photon
calcium
imaging
mouse
V1
method
to
identify
mRNA
for
72
selected
genes
ex
slices.
classified
imaged
layers
1–3
into
three-level
hierarchy
5
subclasses,
11
types
and
35
using
previously
defined
clusters
3
.
Responses
stimuli
differed
significantly
only
between
cells
Sncg
subclass
uniformly
suppressed,
other
subclasses
predominantly
excited.
Modulation
state
at
all
hierarchical
levels
could
be
largely
predicted
from
first
principal
component,
also
correlations
simultaneously
recorded
cells.
Inhibitory
fired
more
resting,
oscillatory
states
had
smaller
fraction
their
axonal
projections
layer
1,
narrower
spikes,
lower
input
resistance
weaker
adaptation
as
determined
vitro
7
expressed
cholinergic
receptors.
Subtypes
during
arousal
opposite
properties.
Thus,
simple
principle
may
explain
how
shape
state-dependent
processing.
Annual Review of Biochemistry,
Год журнала:
2021,
Номер
90(1), С. 507 - 534
Опубликована: Июнь 20, 2021
Mechanosensation
is
the
ability
to
detect
dynamic
mechanical
stimuli
(e.g.,
pressure,
stretch,
and
shear
stress)
essential
for
a
wide
variety
of
processes,
including
our
sense
touch
on
skin.
How
detected
transduced
at
molecular
level
has
proved
be
one
great
mysteries
sensory
biology.
A
major
breakthrough
occurred
in
2010
with
discovery
family
mechanically
gated
ion
channels
that
were
coined
PIEZOs.
The
last
10
years
investigation
have
provided
wealth
information
about
functional
roles
mechanisms
these
molecules.
Here
we
focus
PIEZO2,
two
PIEZO
proteins
found
humans
other
mammals.
We
review
how
work
molecular,
cellular,
systems
levels
over
past
decade
transformed
understanding
led
unexpected
insights
into
types
mechanosensation
beyond
Cell,
Год журнала:
2023,
Номер
186(16), С. 3386 - 3399.e15
Опубликована: Авг. 1, 2023
The
gastrointestinal
tract
is
in
a
state
of
constant
motion.
These
movements
are
tightly
regulated
by
the
presence
food
and
help
digestion
mechanically
breaking
down
propelling
gut
content.
Mechanical
sensing
thought
to
be
essential
for
regulating
motility;
however,
identity
neuronal
populations,
molecules
involved,
functional
consequences
this
sensation
unknown.
Here,
we
show
that
humans
lacking
PIEZO2
exhibit
impaired
bowel
motility.
Piezo2
mouse
dorsal
root,
but
not
nodose
ganglia
required
sense
content,
activity
slows
transit
rates
stomach,
small
intestine,
colon.
Indeed,
directly
detect
colon
distension
vivo.
Our
study
unveils
mechanosensory
mechanisms
regulate
luminal
contents
throughout
gut,
which
critical
process
ensure
proper
digestion,
nutrient
absorption,
waste
removal.
Cell,
Год журнала:
2024,
Номер
187(6), С. 1508 - 1526.e16
Опубликована: Март 1, 2024
Dorsal
root
ganglia
(DRG)
somatosensory
neurons
detect
mechanical,
thermal,
and
chemical
stimuli
acting
on
the
body.
Achieving
a
holistic
view
of
how
different
DRG
neuron
subtypes
relay
neural
signals
from
periphery
to
CNS
has
been
challenging
with
existing
tools.
Here,
we
develop
curate
mouse
genetic
toolkit
that
allows
for
interrogating
properties
functions
distinct
cutaneous
targeting
subtypes.
These
tools
have
enabled
broad
morphological
analysis,
which
revealed
axon
arborization
areas
branching
patterns
transcriptionally
Moreover,
in
vivo
physiological
analysis
each
subtype
threshold
range
responses
mechanical
and/or
thermal
stimuli.
findings
support
model
morphologically
physiologically
sensory
tile
stimulus
space
collectively
encode
wide
natural