A fast and responsive voltage indicator with enhanced sensitivity for unitary synaptic events
Neuron,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 1, 2024
Язык: Английский
Mitochondrial dysfunction drives a neuronal exhaustion phenotype in methylmalonic aciduria
Communications Biology,
Год журнала:
2025,
Номер
8(1)
Опубликована: Март 11, 2025
Abstract
Methylmalonic
aciduria
(MMA)
is
an
inborn
error
of
metabolism
resulting
in
loss
function
the
enzyme
methylmalonyl-CoA
mutase
(MMUT).
Despite
acute
and
persistent
neurological
symptoms,
pathogenesis
MMA
central
nervous
system
poorly
understood,
which
has
contributed
to
a
dearth
effective
brain
specific
treatments.
Here
we
utilised
patient-derived
induced
pluripotent
stem
cells
vitro
differentiation
generate
human
neuronal
model
MMA.
We
reveal
strong
evidence
mitochondrial
dysfunction
caused
by
deficiency
MMUT
patient
neurons.
By
employing
patch-clamp
electrophysiology,
targeted
metabolomics,
bulk
transcriptomics,
expose
altered
state
excitability,
exacerbated
application
dimethyl-2-oxoglutarate,
suggest
may
be
connected
metabolic
rewiring.
Our
work
provides
first
driven
MMA,
through
our
comprehensive
characterisation
this
paradigmatic
model,
enables
steps
identifying
therapies.
Язык: Английский
A deep learning framework for automated and generalized synaptic event analysis
eLife,
Год журнала:
2024,
Номер
13
Опубликована: Июнь 28, 2024
Quantitative
information
about
synaptic
transmission
is
key
to
our
understanding
of
neural
function.
Spontaneously
occurring
events
carry
fundamental
function
and
plasticity.
However,
their
stochastic
nature
low
signal-to-noise
ratio
present
major
challenges
for
the
reliable
consistent
analysis.
Here,
we
introduce
miniML,
a
supervised
deep
learning-based
method
accurate
classification
automated
detection
spontaneous
events.
Comparative
analysis
using
simulated
ground-truth
data
shows
that
miniML
outperforms
existing
event
methods
in
terms
both
precision
recall.
enables
precise
quantification
electrophysiological
recordings.
We
demonstrate
learning
approach
generalizes
easily
diverse
preparations,
different
optical
recording
techniques,
across
animal
species.
provides
not
only
comprehensive
robust
framework
automated,
reliable,
standardized
events,
but
also
opens
new
avenues
high-throughput
investigations
dysfunction.
Язык: Английский