Cells,
Journal Year:
2022,
Volume and Issue:
11(3), P. 396 - 396
Published: Jan. 24, 2022
GABA
depolarizes
and
often
excites
immature
neurons
in
all
animal
species
brain
structures
investigated
due
to
a
developmentally
regulated
reduction
intracellular
chloride
concentration
([Cl-]i)
levels.
The
control
of
[Cl-]i
levels
is
mediated
by
the
cotransporters
NKCC1
KCC2,
former
usually
importing
latter
exporting
it.
polarity
shift
has
been
extensively
validated
several
experimental
conditions
using
importer
antagonist
bumetanide.
In
spite
an
intrinsic
heterogeneity,
this
abolished
many
associated
with
developmental
disorders
including
autism,
Rett
syndrome,
fragile
X
or
maternal
immune
activation.
Using
bumetanide,
EMA-
FDA-approved
agent,
clinical
trials
have
shown
promising
results
expected
side
effects.
Kaila
et
al.
repeatedly
challenged
these
observations.
Here,
we
reply
recent
reviews
stressing
that
solidly
accepted
scientific
community
as
major
discovery
understand
development
bumetanide
effects
trials.
Spontaneous
activity
drives
the
establishment
of
appropriate
connectivity
in
different
circuits
during
brain
development.
In
mouse
primary
visual
cortex,
two
distinct
patterns
spontaneous
occur
before
vision
onset:
local
low-synchronicity
events
originating
retina
and
global
high-synchronicity
cortex.
We
sought
to
determine
contribution
these
jointly
organize
network
through
activity-dependent
plasticity
rules.
postulated
that
shape
cortical
input
selectivity
topography,
while
homeostatically
regulate
connection
strength.
However,
generate
robust
selectivity,
we
found
should
adapt
their
amplitude
history
preceding
activation.
confirmed
this
prediction
by
analyzing
vivo
activity.
The
predicted
adaptation
leads
sparsification
on
a
slower
timescale
development,
demonstrating
remarkable
capacity
developing
sensory
cortex
acquire
sensitivity
inputs
after
eye-opening.
Cell Reports,
Journal Year:
2022,
Volume and Issue:
38(13), P. 110568 - 110568
Published: March 1, 2022
GABAergic
signaling
provides
inhibitory
stabilization
and
spatiotemporally
coordinates
the
firing
of
recurrently
connected
excitatory
neurons
in
mature
cortical
circuits.
Inhibition
thus
enables
self-generated
neuronal
activity
patterns
that
underlie
various
aspects
sensation
cognition.
In
this
review,
we
aim
to
provide
a
conceptual
framework
describing
how
when
GABA-releasing
interneurons
acquire
their
network
functions
during
development.
Focusing
on
developing
visual
neocortex
hippocampus
mice
rats
vivo,
hypothesize
at
onset
patterned
activity,
glutamatergic
are
stable
by
themselves
is
not
yet
functional.
We
review
important
milestones
development
illustrate
cell-type-specific
strengthening
synaptic
inhibition
toward
eye
opening
shapes
dynamics
allows
cortex
progressively
disengage
from
extra-cortical
drive.
translate
human
discuss
clinical
implications
for
treatment
neonatal
seizures.
Cells,
Journal Year:
2022,
Volume and Issue:
11(3), P. 396 - 396
Published: Jan. 24, 2022
GABA
depolarizes
and
often
excites
immature
neurons
in
all
animal
species
brain
structures
investigated
due
to
a
developmentally
regulated
reduction
intracellular
chloride
concentration
([Cl-]i)
levels.
The
control
of
[Cl-]i
levels
is
mediated
by
the
cotransporters
NKCC1
KCC2,
former
usually
importing
latter
exporting
it.
polarity
shift
has
been
extensively
validated
several
experimental
conditions
using
importer
antagonist
bumetanide.
In
spite
an
intrinsic
heterogeneity,
this
abolished
many
associated
with
developmental
disorders
including
autism,
Rett
syndrome,
fragile
X
or
maternal
immune
activation.
Using
bumetanide,
EMA-
FDA-approved
agent,
clinical
trials
have
shown
promising
results
expected
side
effects.
Kaila
et
al.
repeatedly
challenged
these
observations.
Here,
we
reply
recent
reviews
stressing
that
solidly
accepted
scientific
community
as
major
discovery
understand
development
bumetanide
effects
trials.
