The FASEB Journal,
Journal Year:
2025,
Volume and Issue:
39(8)
Published: April 25, 2025
ABSTRACT
Angelman
syndrome
(AS)
is
a
severe
neurodevelopmental
disorder
with
no
effective
therapies.
Most
of
the
behavioral
deficits
observed
in
AS
patients
arise
from
absence
ubiquitin
protein
ligase
E3A
(UBE3A)
brain
during
development,
driven
by
loss
maternally
expressed
UBE3A
and
silencing
paternal
copy
this
gene
through
imprinting.
Safe
therapies
aiming
at
restoring
expression
early
human
life
are
currently
lacking.
In
study,
we
investigated
whether
octanoic
acid
(OA),
medium‐chain
fatty
acid,
could
unsilence
Ube3a
allele
neurons
ameliorate
defects
murine
model
AS.
To
end,
m−/p+
m+/pYFP
mice,
as
well
their
wild‐type
littermates,
were
fed
either
control
or
OA‐supplemented
diet
postnatal
day
0
adulthood,
improvements
AS‐related
cellular
characterized.
We
demonstrate
that
dietary
intake
OA
activates
silenced,
improves
select
phenotypes
mice.
further
show
downregulation
topoisomerase
II
beta
restoration
dendritic
spine
development
may
underlie
unsilencing
animals,
respectively.
Together,
our
findings
suggest
supplementation
serve
an
early,
safe,
clinically
feasible
therapeutic
strategy
for
reactivation
Science,
Journal Year:
2023,
Volume and Issue:
380(6644), P. 543 - 551
Published: May 4, 2023
The
ability
to
form
precise,
episodic
memories
develops
with
age,
young
children
only
able
gist-like
that
lack
precision.
cellular
and
molecular
events
in
the
developing
hippocampus
underlie
emergence
of
episodic-like
memory
are
unclear.
In
mice,
absence
a
competitive
neuronal
engram
allocation
process
immature
precluded
formation
sparse
engrams
precise
until
fourth
postnatal
week,
when
inhibitory
circuits
mature.
This
age-dependent
shift
precision
involved
functional
maturation
parvalbumin-expressing
interneurons
subfield
CA1
through
assembly
extracellular
perineuronal
nets,
which
is
necessary
sufficient
for
onset
allocation,
formation,
Annual Review of Neuroscience,
Journal Year:
2024,
Volume and Issue:
47(1), P. 1 - 20
Published: Feb. 16, 2024
Auditory
processing
in
mammals
begins
the
peripheral
inner
ear
and
extends
to
auditory
cortex.
Sound
is
transduced
from
mechanical
stimuli
into
electrochemical
signals
of
hair
cells,
which
relay
information
via
primary
neurons
cochlear
nuclei.
Information
subsequently
processed
superior
olivary
complex,
lateral
lemniscus,
inferior
colliculus
projects
cortex
medial
geniculate
body
thalamus.
Recent
advances
have
provided
valuable
insights
development
functioning
structures,
complementing
our
understanding
physiological
mechanisms
underlying
processing.
This
comprehensive
review
explores
genetic
required
for
system
cochlea
We
highlight
transcription
factors
other
genes
with
key
recurring
interacting
roles
guiding
organization.
Understanding
these
gene
regulatory
networks
holds
promise
developing
novel
therapeutic
strategies
hearing
disorders,
benefiting
millions
globally.
Neuron,
Journal Year:
2024,
Volume and Issue:
112(7), P. 1060 - 1080
Published: Feb. 14, 2024
Human
episodic
memory
is
not
functionally
evident
until
about
2
years
of
age
and
continues
to
develop
into
the
school
years.
Behavioral
studies
have
elucidated
this
developmental
timeline
its
constituent
processes.
In
tandem,
lesion
neurophysiological
in
non-human
primates
rodents
identified
key
neural
substrates
circuit
mechanisms
that
may
underlie
development.
Despite
progress,
collaborative
efforts
between
psychologists
neuroscientists
remain
limited,
hindering
progress.
Here,
we
seek
bridge
human
development
research
by
offering
a
comparative
review
using
humans,
primates,
rodents.
We
highlight
critical
theoretical
methodological
issues
limit
cross-fertilization
propose
common
framework,
adaptable
different
species,
facilitate
cross-species
endeavors.
Early
electrophysiological
brain
oscillations
recorded
in
preterm
babies
and
newborn
rodents
are
initially
mostly
driven
by
bottom-up
sensorimotor
activity
only
later
can
detach
from
external
inputs.
This
is
a
hallmark
of
most
developing
areas,
including
the
hippocampus,
which,
adult
brain,
functions
integrating
inputs
onto
internal
dynamics.
Such
developmental
disengagement
likely
fundamental
step
for
proper
development
cognitive
models.
Despite
its
importance,
timeline
circuit
basis
this
remain
unknown.
To
address
issue,
we
have
investigated
daily
evolution
CA1
dynamics
underlying
circuits
during
first
two
postnatal
weeks
mouse
using
two-photon
calcium
imaging
non-anesthetized
pups.
We
show
that
week
ends
with
an
abrupt
shift
representation
self-motion
CA1.
Indeed,
pyramidal
cells
switch
activated
to
inhibited
self-generated
movements
at
end
week,
whereas
majority
GABAergic
neurons
positively
modulated
throughout
period.
rapid
occurs
within
2
days
follows
anatomical
functional
surge
local
somatic
innervation.
The
observed
change
consistent
two-population
model
undergoing
strengthening
inhibition.
propose
transition
inaugurates
emergence
hippocampal
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 25, 2024
Abstract
Sharp
wave-ripples
(SPW-Rs)
are
a
hippocampal
network
phenomenon
critical
for
memory
consolidation
and
planning.
SPW-Rs
have
been
extensively
studied
in
the
adult
brain,
yet
their
developmental
trajectory
is
poorly
understood.
While
SPWs
recorded
rodents
shortly
after
birth,
time
point
mechanisms
of
ripple
emergence
still
unclear.
Here,
we
combine
vivo
electrophysiology
with
optogenetics
chemogenetics
4
to
12-day-old
mice
address
this
knowledge
gap.
We
show
that
ripples
robustly
detected
induced
by
light
stimulation
channelrhodopsin-2-transfected
CA1
pyramidal
neurons
only
from
postnatal
day
10
onwards.
Leveraging
spiking
neural
model,
mechanistically
link
maturation
inhibition
emergence.
corroborate
these
findings
reducing
rate
upon
chemogenetic
silencing
interneurons.
Finally,
early
elicit
more
robust
prefrontal
cortex
response
than
lacking
ripples.
Thus,
development
promotes
