Toward Optogenetic Hearing Restoration
Annual Review of Neuroscience,
Год журнала:
2024,
Номер
47(1), С. 103 - 121
Опубликована: Апрель 10, 2024
The
cochlear
implant
(CI)
is
considered
the
most
successful
neuroprosthesis
as
it
enables
speech
comprehension
in
majority
of
million
otherwise
deaf
patients.
In
hearing
by
electrical
stimulation
auditory
nerve,
broad
spread
current
from
each
electrode
acts
a
bottleneck
that
limits
transfer
sound
frequency
information.
Hence,
there
remains
major
unmet
medical
need
for
improving
quality
with
CIs.
Recently,
optogenetic
cochlea
has
been
suggested
an
alternative
approach
restoration.
Cochlear
optogenetics
promises
to
more
information,
hence
hearing,
light
can
conveniently
be
confined
space
activate
nerve
within
smaller
tonotopic
ranges.
this
review,
we
discuss
latest
experimental
and
technological
developments
restoration
outline
remaining
challenges
en
route
clinical
translation.
Язык: Английский
Intracellular microbial rhodopsin-based optogenetics to control metabolism and cell signaling
Chemical Society Reviews,
Год журнала:
2024,
Номер
53(7), С. 3327 - 3349
Опубликована: Янв. 1, 2024
Organelle
optogenetics
is
an
approach
to
control
cell
physiology
by
targeted
expression
of
microbial
rhodopsins
in
membranes
subcellular
organelles.
Язык: Английский
Genetically‐targeted control of the spinal cord and peripheral nervous system
Journal of intelligent medicine.,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 22, 2025
Abstract
Genetically‐targeted
neuromodulation,
such
as
opto‐
or
chemogenetics,
is
important
for
cell‐type
specific
neuromodulation
different
applications.
Modulating
peripheral
nerves
a
daunting
task
due
to
the
wide
variety
of
constraints
in
periphery,
size,
location,
and
relative
distance
other
nerves.
This
has
resulted
many
researchers
developing
innovative
solutions
modulate
nerves,
including
types
light‐emitting
devices
optogenetics,
ligands
designer
drugs
(DREADDs)
use
nanotechnology.
Although
spinal
cord
part
central
nervous
system,
it
often
site
stimulation
modulating
function
periphery
anatomy
same
obstacles
modulation
review
summarizes
current
efforts
genetically‐targeted
grouped
by
applications,
going
through
major
areas
which
advancements
have
been
made.
We
focus
on
vivo
research
rodents
but
also
briefly
discuss
work
nonhuman
primates
(NHPs).
Some
clinical
translation,
long‐term
adeno‐associated
virus
(AAV)
safety,
are
discussed
some
noninvasive,
nonspecific
technologies
mentioned.
Язык: Английский
Frequency Following Responses to Electric Cochlear Stimulation in an Animal Model
Journal of the Association for Research in Otolaryngology,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 21, 2025
Abstract
Purpose
Present-day
cochlear-implant
(CI)
users
can
achieve
high
levels
of
speech
reception
in
quiet
surroundings.
Nevertheless,
sensitivity
to
the
temporal
pitch
sounds
is
limited,
which
contributes
deficits
amid
multiple
talkers
and
appreciation
musical
melodies.
Short-term,
invasive
neurophysiological
studies
animals
have
demonstrated
limitations
neural
phase
locking
tonotopic
range
auditory
pathway
that
activated
by
CIs.
It
remains
an
open
question,
however,
whether
those
account
for
perceptual
animal
species,
let
alone
human
CI
users.
For
reason,
we
evaluated
non-invasive
recordings
from
cats
chronically
implanted
with
a
CI.
Methods
Ten
deafened
(eight
female)
were
version
clinical
array.
The
electrically
evoked
frequency
following
response
(eFFRs)
was
recorded
scalps
sedated
at
≥
10
weeks
post-implantation.
Stimuli
consisted
constant-amplitude
electrical
pulse
trains
rates
~
40
640
pulses
per
second.
Results
Recordings
eFFR
robust
responses
synchronized
across
all
stimulus
rates.
Analyses
amplitude
transfer
functions
confirmed
eFFR,
as
its
normal-hearing
counterpart,
originates
subcortical
cortical
generators.
slopes
segments
revealed
stimulus-to-response
latencies
generators
dominated
restricted
ranges
Those
rate
must
coincide
limits
putative
successive
neuroaxis
could
inform
our
understanding
acuity.
Conclusion
here
model
provides
valuable
measure
processing
electric
cochlear
stimulation
be
related
ongoing
measures
same
well-suited
evaluate
novel
modes
prosthesis
enhancing
Язык: Английский
Decreasing the physical gap in the neural-electrode interface and related concepts to improve cochlear implant performance
Frontiers in Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Июль 24, 2024
Cochlear
implants
(CI)
represent
incredible
devices
that
restore
hearing
perception
for
those
with
moderate
to
profound
sensorineural
loss.
However,
the
ability
of
a
CI
complex
auditory
function
is
limited
by
number
perceptually
independent
spectral
channels
provided.
A
major
contributor
this
limitation
physical
gap
between
electrodes
and
target
spiral
ganglion
neurons
(SGNs).
In
order
stimulate
SGNs
more
precisely,
thus
better
approximate
natural
hearing,
new
methodologies
need
be
developed
decrease
gap,
(i.e.,
transitioning
CIs
from
far-field
near-field
device).
review,
strategies
aimed
at
improving
neural-electrode
interface
are
discussed
in
terms
magnitude
impact
they
could
have
work
needed
implement
them.
Ongoing
research
suggests
current
clinical
efforts
limit
CI-related
immune
response
holds
great
potential
device
performance.
This
eradicate
dense,
fibrous
capsule
surrounding
electrode
enhance
preservation
cochlear
architecture,
including
SGNs.
long
term,
however,
optimized
future
will
likely
induce
guide
outgrowth
peripheral
process
closer
proximity
hearing.
its
infancy;
it
remains
seen
which
(surface
patterning,
small
molecule
release,
hydrogel
coating,
etc.)
enable
approach.
Additionally,
these
optimizing
translate
other
neural
prostheses,
face
similar
issues.
Язык: Английский
Efficient and sustained optogenetic control of nervous and cardiac systems
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 18, 2023
Abstract
Optogenetic
control
of
cells
is
a
key
life
sciences
method
and
promises
novel
therapies.
Here
we
report
on
ChReef,
an
improved
variant
the
channelrhodopsin
ChRmine.
ChReef
offers
minimal
photocurrent
desensitization,
unitary
conductance
80
fS
closing
kinetics
30
ms,
which
together
enable
reliable
optogenetic
at
low
light
levels
(nano-Joule)
with
good
temporal
fidelity
allows
sustained
stimulation.
We
demonstrate
efficient
red-light
pacing
depolarization
block
ChReef-expressing
cardiomyocyte
clusters.
Towards
clinical
application
used
AAV-based
gene
transfer
to
express
in
retinal
ganglion
where
it
restores
visual
function
blind
mice
sources
as
weak
iPad
screen.
Toward
hearing
restoration,
enables
stimulation
auditory
pathway
rodents
non-human
primates
nano-Joule
threshold
enabling
frequency-specific
by
LED-based
optical
cochlear
implants.
Thus,
bears
great
potential
for
application.
Язык: Английский
Devising a framework of optogenetic coding in the auditory pathway: Insights from auditory midbrain recordings
Brain stimulation,
Год журнала:
2023,
Номер
16(5), С. 1486 - 1500
Опубликована: Сен. 1, 2023
Cochlear
implants
(CIs)
restore
activity
in
the
deafened
auditory
system
via
electrical
stimulation
of
nerve.
As
spread
electric
current
biological
tissues
is
rather
broad,
spectral
information
provided
by
CIs
limited.
Optogenetic
nerve
has
been
suggested
for
artificial
sound
coding
with
improved
selectivity,
as
light
can
be
conveniently
confined
space.
Yet,
foundations
optogenetic
strategies
remain
to
established.
Here,
we
parametrized
stimulus-response-relationships
pathway
gerbils
stimulation.
Upon
activation
waveguide-based
spiral
ganglion,
recorded
neuronal
midbrain,
which
neural
representations
spectral,
temporal,
and
intensity
found.
Screening
a
wide
range
optical
stimuli
taking
properties
CI
emitters
into
account,
aimed
optimize
stimulus
paradigms
potent
energy-efficient
pathway.
We
report
that
efficient
builds
on
integration
millisecond
built
from
microsecond
pulses,
optimally
accommodate
power-efficient
laser
diode
operation.
Moreover,
performed
an
activity-level-dependent
comparison
acoustic
order
estimate
dynamic
maximal
amenable
single
channel
encoding,
indicate
it
complies
well
speech
comprehension
typical
conversation
(65
dB).
Our
results
provide
first
framework
development
future
hearing
restoration.
Язык: Английский
En route to sound coding strategies for optical cochlear implants
iScience,
Год журнала:
2023,
Номер
26(10), С. 107725 - 107725
Опубликована: Авг. 26, 2023
Hearing
loss
is
the
most
common
human
sensory
deficit.
Severe-to-complete
sensorineural
hearing
often
treated
by
electrical
cochlear
implants
(eCIs)
bypassing
dysfunctional
or
lost
hair
cells
direct
stimulation
of
auditory
nerve.
The
wide
current
spread
from
each
intracochlear
electrode
array
contact
activates
large
sets
tonotopically
organized
neurons
limiting
spectral
selectivity
sound
coding.
Despite
many
efforts,
an
increase
in
number
independent
eCI
channels
seems
impossible
to
achieve.
Light,
which
can
be
better
confined
space
than
electric
may
help
optical
(oCIs)
overcome
shortcomings.
In
this
review,
we
present
state
optogenetic
encoding.
We
highlight
coding
strategy
development
capitalizing
on
that
requires
fine-grained,
fast,
and
power-efficient
real-time
processing
controlling
dozens
microscale
emitters
as
emerging
research
area.
Язык: Английский
Optogenetically modified human embryonic stem cell-derived otic neurons establish functional synaptic connection with cochlear nuclei
Journal of Tissue Engineering,
Год журнала:
2024,
Номер
15
Опубликована: Янв. 1, 2024
Spiral
ganglia
neurons
(SGNs)
impairment
can
cause
deafness.
One
important
therapeutic
approach
involves
utilizing
stem
cells
to
restore
impaired
auditory
circuitry.
Nevertheless,
the
inadequate
implementation
of
research
methodologies
poses
a
challenge
in
accurately
assessing
functionality
derived
within
circuit.
Here,
we
describe
novel
method
for
converting
human
embryonic
(hESCs)
into
otic
(ONs)
and
assess
their
functional
connectivity
using
an
optogenetic
with
or
organotypic
slice
rat
cochlear
nucleus
(CN)
coculture.
Embryonic
cell-derived
(eONs)
exhibited
SGN
marker
expression
generated
synaptic
connection
when
cocultured
(CNNs).
Synapsin
1
VGLUT
are
found
brain
slices,
where
eONs
projected
processes
during
coculture
CN
slices.
Action
potential
spikes
I
Na+
/I
K+
CNNs
increased
tandem
light
stimulations
eONs.
These
findings
provide
further
evidence
that
may
be
candidate
source
treat
SGN-deafness.
Язык: Английский
Improved optogenetic modification of the spiral ganglion neurons for future optical cochlear implants
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 12, 2024
Abstract
Optogenetic
stimulation
has
become
a
promising
approach
for
restoring
lost
body
function.
For
example,
partial
restoration
of
vision
been
achieved
in
blind
patient
and
proof-of-concept
demonstrated
optogenetic
hearing
rodents.
In
order
to
prepare
clinical
translation
restoration,
efficient
safe
modification
spiral
ganglion
neurons
(SGNs)
the
mature
cochlea
remains
be
developed.
Here,
we
established
microcatheter-based
administration
adeno-associated
virus
(AAV)
scala
tympani
Mongolian
gerbils
compared
it
previously
developed
AAV-injection
into
ganglion.
We
probed
potential
AAV-PHP.S
capsid
express
channelrhodopsins
(ChRs)
under
control
human
synapsin
promotor
SGNs
deafened
gerbils.
Using
microcatheter
approach,
but
not
with
AAV-modiolus
injection,
reliable
ChR
expression
SGN
enabling
auditory
pathway
80%
treated
animals.
Yet,
efficiency
transduction
was
modest
only
∼30%
ChR-expressing
SGNs.
Moreover,
encountered
off-target
hair
cells
both
approaches,
central
nervous
system
using
administration.
Comparing
brainstem
responses
without
cell
confirmed
that
were
primary
site
pathway.
Язык: Английский