Cerebellar contributions to dystonia: unraveling the role of Purkinje cells and cerebellar nuclei
Dystonia,
Год журнала:
2025,
Номер
4
Опубликована: Фев. 17, 2025
Dystonias
are
a
group
of
neurodegenerative
disorders
that
result
in
altered
physiology
associated
with
motor
movements.
Both
the
basal
ganglia
and
cerebellum,
brain
regions
involved
learning,
sensory
perception
integration,
reward,
have
been
implicated
pathology
dystonia,
but
cellular
subcellular
mechanisms
remain
diverse
for
some
forms
elusive.
The
goal
current
review
is
to
summarize
recent
evidence
cerebellar
involvement
different
subtypes
dystonia
focus
on
Purkinje
cell
(PC)
nuclei
(CN)
dysfunction,
find
commonalities
could
lay
groundwork
future
development
therapeutics
patients
dystonia.
Here
we
will
briefly
discuss
physical
functional
connections
between
cerebellum
how
these
contribute
dystonic
symptoms.
We
proceed
use
human
animal
model
data
contributions
types
specific
dystonias
movement
where
secondary
symptom.
Ultimately,
suggest
PC
CN
irregularity
be
locus
through
impaired
calcium
dynamics.
Язык: Английский
Characterization of direct Purkinje cell outputs to the brainstem
Опубликована: Фев. 10, 2025
Purkinje
cells
(PCs)
primarily
project
to
cerebellar
nuclei
but
also
directly
innervate
the
brainstem.
Some
PC-brainstem
projections
have
been
described
previously,
most
not
thoroughly
characterized.
Here
we
use
a
PC-specific
cre
line
anatomically
and
electrophysiologically
characterize
PC
synapses
are
surprisingly
widespread,
with
highest
densities
found
in
vestibular
parabrachial
nuclei.
However,
there
pronounced
regional
differences
synaptic
within
both
Large
optogenetically-evoked
PC-IPSCs
preferentially
observed
subregions
of
synapses,
suggesting
that
PCs
selectively
influence
these
areas
behaviors
they
regulate.
Unexpectedly,
pontine
central
gray
nearby
subnuclei
contained
low
density
large
small
fraction
cells.
We
combined
electrophysiological
recordings
immunohistochemistry
assess
molecular
identities
two
putative
targets:
onto
mesencephalic
trigeminal
neurons
were
even
though
close
proximity
boutons.
locus
coeruleus
exceedingly
rare
or
absent,
previous
studies
concluded
major
input
neurons.
The
availability
highly
selective
for
allowed
us
study
functional
while
avoiding
complications
can
accompany
viral
approaches.
conclude
numerous
brainstem
nuclei,
only
inhibit
many
This
suggests
target
cell
types
specific
behavioral
roles
regions.
Язык: Английский
Characterization of direct Purkinje cell outputs to the brainstem
eLife,
Год журнала:
2025,
Номер
13
Опубликована: Фев. 27, 2025
Purkinje
cells
(PCs)
primarily
project
to
cerebellar
nuclei
but
also
directly
innervate
the
brainstem.
Some
PC-brainstem
projections
have
been
described
previously,
most
not
thoroughly
characterized.
Here,
we
use
a
PC-specific
cre
line
anatomically
and
electrophysiologically
characterize
PC
synapses
are
surprisingly
widespread,
with
highest
densities
found
in
vestibular
parabrachial
nuclei.
However,
there
pronounced
regional
differences
synaptic
within
both
Large
optogenetically
evoked
PC-IPSCs
preferentially
observed
subregions
of
putative
boutons,
suggesting
that
PCs
selectively
influence
these
areas
behaviors
they
regulate.
Unexpectedly,
pontine
central
gray
nearby
subnuclei
contained
low
density
large
small
fraction
cells.
We
combined
electrophysiological
recordings
immunohistochemistry
assess
molecular
identities
two
potential
targets:
onto
mesencephalic
trigeminal
neurons
were
even
though
close
proximity
boutons;
locus
coeruleus
exceedingly
rare
or
absent,
previous
studies
concluded
major
input
neurons.
The
availability
highly
selective
for
allowed
us
study
functional
synapses,
while
avoiding
complications
can
accompany
viral
approaches.
conclude
numerous
brainstem
nuclei,
many
strongly
inhibit
This
suggests
target
cell
types
specific
behavioral
roles
Язык: Английский
Anatomy, histology, physiology, and connectivity of the cerebellum
Elsevier eBooks,
Год журнала:
2025,
Номер
unknown, С. 1 - 19
Опубликована: Янв. 1, 2025
Язык: Английский
Purkinje Cell spike patterns do not correlate with nuclei cell spike patterns in mouse models for cerebellar disease
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Май 21, 2025
Cerebellar
dysfunction
causes
various
movement
disorders,
including
ataxia,
dystonia,
and
tremor.
Previous
work
demonstrated
that
spike
patterns
in
cerebellar
nuclei
neurons
were
distinct
between
different
disorder
mouse
models.
However,
often
these
changes
arise
from
neural
the
cortex,
through
misfiring,
miswiring,
or
degenerating
Purkinje
cells.
Even
though
cells
form
sole
output
their
information
is
relayed
to
other
regions
of
motor
network
via
make
GABAergic
synapses
onto
cells,
it
assumed
cell
result
inverse
patterns.
Here,
we
test
this
hypothesis
by
answering
question
whether
a
reliable
relationship
exists.
Single-cell,
vivo
electrophysiology
recordings
both
types
six
models
for
disorders
analyzed
according
parameters
relating
rate
irregularity.
We
investigated
correlated
with
found
some
firing
irregularity
positively
but
no
-
particularly
was
observed
rate.
Overall,
study
begins
illuminate
activity
disease
state
more
complex
unpredictable.
The
data
suggest
cannot
accurately
predict
changes,
which
ultimately
drive
states.
Our
findings
underscore
importance
studying
function
disease,
as
lack
can
mask
disease-causing
Язык: Английский
A dual Purkinje cell rate and synchrony code sculpts reach kinematics
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Июль 12, 2023
Abstract
Cerebellar
Purkinje
cells
(PCs)
encode
movement
kinematics
in
their
population
firing
rates.
Firing
rate
suppression
is
hypothesized
to
disinhibit
neurons
the
cerebellar
nuclei,
promoting
adaptive
adjustments.
Debates
persist,
however,
about
whether
a
second
disinhibitory
mechanism,
PC
simple
spike
synchrony,
relevant
code.
We
addressed
this
question
by
relating
and
synchrony
patterns
recorded
with
high
density
probes,
mouse
reach
kinematics.
discovered
behavioral
correlates
of
that
align
known
causal
relationship
between
activity
output.
Reach
deceleration
was
positively
correlated
both
decreases
consistent
mechanisms
disinhibiting
target
neurons,
which
are
adjust
velocity.
Direct
tests
contribution
each
coding
scheme
nuclear
using
dynamic
clamp,
combining
physiological
ex
vivo,
confirmed
levels
highly
facilitatory
for
firing.
These
findings
suggest
collaborate
exert
fine
control
movement.
Язык: Английский
The cerebellar nuclei take center stage
Current Opinion in Behavioral Sciences,
Год журнала:
2024,
Номер
57, С. 101362 - 101362
Опубликована: Март 23, 2024
Язык: Английский
Characterization of direct Purkinje cell outputs to the brainstem
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 18, 2024
Abstract
Purkinje
cells
(PCs)
primarily
project
to
cerebellar
nuclei
but
also
directly
innervate
the
brainstem.
Some
PC-brainstem
projections
have
been
described
previously,
most
not
thoroughly
characterized.
Here
we
use
a
PC-specific
cre
line
anatomically
and
electrophysiologically
characterize
PC
synapses
are
surprisingly
widespread,
with
highest
densities
found
in
vestibular
parabrachial
nuclei.
However,
there
pronounced
regional
differences
synaptic
within
both
Large
optogenetically-evoked
PC-IPSCs
preferentially
observed
subregions
of
synapses,
suggesting
that
PCs
selectively
influence
these
areas
behaviors
they
regulate.
Unexpectedly,
pontine
central
gray
nearby
subnuclei
contained
low
density
large
small
fraction
cells.
We
combined
electrophysiological
recordings
immunohistochemistry
assess
molecular
identities
two
putative
targets:
onto
mesencephalic
trigeminal
neurons
were
even
though
close
proximity
boutons.
locus
coeruleus
exceedingly
rare
or
absent,
previous
studies
concluded
major
input
neurons.
The
availability
highly
selective
for
allowed
us
study
functional
while
avoiding
complications
can
accompany
viral
approaches.
conclude
numerous
brainstem
nuclei,
only
inhibit
many
This
suggests
target
cell
types
specific
behavioral
roles
regions.
Язык: Английский
Characterization of direct Purkinje cell outputs to the brainstem
Опубликована: Окт. 17, 2024
Purkinje
cells
(PCs)
primarily
project
to
cerebellar
nuclei
but
also
directly
innervate
the
brainstem.
Some
PC-brainstem
projections
have
been
described
previously,
most
not
thoroughly
characterized.
Here
we
use
a
PC-specific
cre
line
anatomically
and
electrophysiologically
characterize
PC
synapses
are
surprisingly
widespread,
with
highest
densities
found
in
vestibular
parabrachial
nuclei.
However,
there
pronounced
regional
differences
synaptic
within
both
Large
optogenetically-evoked
PC-IPSCs
preferentially
observed
subregions
of
synapses,
suggesting
that
PCs
selectively
influence
these
areas
behaviors
they
regulate.
Unexpectedly,
pontine
central
gray
nearby
subnuclei
contained
low
density
large
small
fraction
cells.
We
combined
electrophysiological
recordings
immunohistochemistry
assess
molecular
identities
targets.
onto
mesencephalic
trigeminal
neurons
were
even
though
close
proximity
boutons.
locus
coeruleus
exceedingly
rare
or
absent,
previous
studies
concluded
major
input
neurons.
The
availability
highly
selective
for
allowed
us
study
functional
while
avoiding
complications
can
accompany
viral
approaches.
conclude
numerous
brainstem
nuclei,
only
inhibit
many
This
suggests
target
cell
types
specific
behavioral
roles
regions.
Язык: Английский
Characterization of direct Purkinje cell outputs to the brainstem
eLife,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 17, 2024
Purkinje
cells
(PCs)
primarily
project
to
cerebellar
nuclei
but
also
directly
innervate
the
brainstem.
Some
PC-brainstem
projections
have
been
described
previously,
most
not
thoroughly
characterized.
Here,
we
use
a
PC-specific
cre
line
anatomically
and
electrophysiologically
characterize
PC
synapses
are
surprisingly
widespread,
with
highest
densities
found
in
vestibular
parabrachial
nuclei.
However,
there
pronounced
regional
differences
synaptic
within
both
Large
optogenetically
evoked
PC-IPSCs
preferentially
observed
subregions
of
putative
boutons,
suggesting
that
PCs
selectively
influence
these
areas
behaviors
they
regulate.
Unexpectedly,
pontine
central
gray
nearby
subnuclei
contained
low
density
large
small
fraction
cells.
We
combined
electrophysiological
recordings
immunohistochemistry
assess
molecular
identities
two
potential
targets:
onto
mesencephalic
trigeminal
neurons
were
even
though
close
proximity
boutons;
locus
coeruleus
exceedingly
rare
or
absent,
previous
studies
concluded
major
input
neurons.
The
availability
highly
selective
for
allowed
us
study
functional
synapses,
while
avoiding
complications
can
accompany
viral
approaches.
conclude
numerous
brainstem
nuclei,
many
strongly
inhibit
This
suggests
target
cell
types
specific
behavioral
roles
Язык: Английский