ENHANCED RESTORATION OF VISUAL CODE AFTER TARGETING ON BIPOLAR CELLS COMPARED TO RETINAL GANGLION CELLS WITH OPTOGENETIC THERAPY
Molecular Therapy,
Год журнала:
2025,
Номер
33(3), С. 1264 - 1281
Опубликована: Янв. 18, 2025
Язык: Английский
Biophysical neural adaptation mechanisms enable artificial neural networks to capture dynamic retinal computation
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 16, 2024
Abstract
Adaptation
is
a
universal
aspect
of
neural
systems
that
changes
circuit
computations
to
match
prevailing
inputs.
These
facilitate
efficient
encoding
sensory
inputs
while
avoiding
saturation.
Conventional
artificial
networks
(ANNs)
have
limited
adaptive
capabilities,
hindering
their
ability
reliably
predict
output
under
dynamic
input
conditions.
Can
embedding
mechanisms
in
ANNs
improve
performance?
To
answer
this
question,
we
develop
new
deep
learning
model
the
retina
incorporates
biophysics
photoreceptor
adaptation
at
front-end
conventional
convolutional
(CNNs).
CNNs
build
on
’Deep
Retina,’
previously
developed
retinal
ganglion
cell
(RGC)
activity.
include
layer
outperform
CNN
models
predicting
male
and
female
primate
rat
RGC
responses
naturalistic
stimuli
local
intensity
large
ambient
illumination.
improved
predictions
result
directly
from
within
phototransduction
cascade.
This
research
underscores
potential
using
them
determine
how
circuits
manage
complexities
natural
are
span
range
light
levels.
Язык: Английский
Cone bipolar cell synapses generate transient versus sustained signals in parallel ON pathways of the mouse retina
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 14, 2024
Abstract
Parallel
processing
is
a
fundamental
organizing
principle
in
the
nervous
system,
and
understanding
how
parallel
neural
circuits
generate
distinct
outputs
from
common
inputs
key
goal
of
neuroscience.
In
mammalian
retina,
divergence
cone
signals
into
multiple
feed-forward
bipolar
cell
pathways
forms
initial
basis
for
retinal
dedicated
to
specific
visual
functions.
Here,
we
used
patch-clamp
electrophysiology,
electron
microscopy
two
photon
imaging
fluorescent
glutamate
sensor
examine
kinetically
responses
arise
transient
versus
sustained
ON
alpha
RGCs
(ON-T
ON-S
RGCs)
mouse
retina.
We
directly
compared
response
properties
these
with
their
presynaptic
partners,
which
identified
using
3D
reconstruction.
Different
subtypes
(type
5i,
type
6
7)
had
indistinguishable
light-driven
whereas
extracellular
around
RGC
dendrites
postsynaptic
excitatory
currents
measured
ON-T
identical
stimuli
probe
cells
were
distinct.
Anatomical
examination
axon
terminals
suggests
subtype-specific
differences
size
synaptic
ribbon-associated
vesicle
pools
may
contribute
kinetics.
Our
findings
indicate
synapses
are
primary
point
pathways.
Язык: Английский
Cone bipolar cell synapses generate transient versus sustained signals in parallel ON pathways of the mouse retina
Опубликована: Авг. 20, 2024
Parallel
processing
is
a
fundamental
organizing
principle
in
the
nervous
system,
and
understanding
how
parallel
neural
circuits
generate
distinct
outputs
from
common
inputs
key
goal
of
neuroscience.
In
mammalian
retina,
divergence
cone
signals
into
multiple
feed-forward
bipolar
cell
pathways
forms
initial
basis
for
retinal
dedicated
to
specific
visual
functions.
Here,
we
used
patch-clamp
electrophysiology,
electron
microscopy
two
photon
imaging
fluorescent
glutamate
sensor
examine
kinetically
responses
arise
transient
versus
sustained
ON
alpha
RGCs
(ON-T
ON-S
RGCs)
mouse
retina.
We
directly
compared
response
properties
these
with
their
presynaptic
partners,
which
identified
using
3D
reconstruction.
Different
subtypes
(type
5i,
type
6
7)
had
indistinguishable
light-driven
whereas
extracellular
around
RGC
dendrites
postsynaptic
excitatory
currents
measured
ON-T
identical
stimuli
probe
cells
were
distinct.
Anatomical
examination
axon
terminals
suggests
subtype-specific
differences
size
synaptic
ribbon-associated
vesicle
pools
may
contribute
kinetics.
Our
findings
indicate
synapses
are
primary
point
pathways.
Язык: Английский
Enhanced restoration of visual code after targeting on bipolar cells compared to retinal ganglion cells with optogenetic therapy
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 23, 2024
ABSTRACT
Optogenetic
therapy
is
a
promising
vision
restoration
method
where
light
sensitive
opsins
are
introduced
to
the
surviving
inner
retina
following
photoreceptor
degeneration.
The
cell
type
targeted
for
opsin
expression
will
likely
influence
quality
of
restored
vision.
However,
like-for-like
pre-clinical
comparison
visual
responses
evoked
equivalent
in
two
major
targets,
ON
bipolar
(ON
BCs)
or
retinal
ganglion
cells
(RGCs),
absent.
We
address
this
deficit
by
comparing
stimulus-response
characteristics
at
single
unit
resolution
and
dorsal
lateral
geniculate
nucleus
(dLGN)
retinally
degenerate
mice
genetically
engineered
express
ReaChR
Grm6-
Brn3c
-expressing
BC
vs
RGCs
respectively).
For
both
targeting
strategies,
we
find
ReaChR-evoked
have
sensitivity
can
encode
contrast
across
different
background
irradiances.
Compared
BCs,
decreased
response
reproducibility
resulted
more
stereotyped
with
reduced
diversity
polarity,
temporal
frequency
tuning.
Recording
ReaChR-driven
visually
intact
retinas
confirmed
that
RGC-targeted
disrupts
feature
selectivity
individual
RGCs.
Our
data
show
while
approaches
restore
impressive
fidelity,
produces
richer
code
better
approaching
wildtype
mice.
Язык: Английский
Cone bipolar cell synapses generate transient versus sustained signals in parallel ON pathways of the mouse retina
Опубликована: Авг. 20, 2024
Parallel
processing
is
a
fundamental
organizing
principle
in
the
nervous
system,
and
understanding
how
parallel
neural
circuits
generate
distinct
outputs
from
common
inputs
key
goal
of
neuroscience.
In
mammalian
retina,
divergence
cone
signals
into
multiple
feed-forward
bipolar
cell
pathways
forms
initial
basis
for
retinal
dedicated
to
specific
visual
functions.
Here,
we
used
patch-clamp
electrophysiology,
electron
microscopy
two
photon
imaging
fluorescent
glutamate
sensor
examine
kinetically
responses
arise
transient
versus
sustained
ON
alpha
RGCs
(ON-T
ON-S
RGCs)
mouse
retina.
We
directly
compared
response
properties
these
with
their
presynaptic
partners,
which
identified
using
3D
reconstruction.
Different
subtypes
(type
5i,
type
6
7)
had
indistinguishable
light-driven
whereas
extracellular
around
RGC
dendrites
postsynaptic
excitatory
currents
measured
ON-T
identical
stimuli
probe
cells
were
distinct.
Anatomical
examination
axon
terminals
suggests
subtype-specific
differences
size
synaptic
ribbon-associated
vesicle
pools
may
contribute
kinetics.
Our
findings
indicate
synapses
are
primary
point
pathways.
Язык: Английский