bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: Aug. 30, 2022
ABSTRACT
During
nervous
system
development,
neurons
choose
synaptic
partners
with
remarkable
specificity;
however,
the
cell-cell
recognition
mechanisms
governing
rejection
of
inappropriate
remain
enigmatic.
Here
we
show
that
mouse
retinal
avoid
using
FLRT2-UNC5
receptor-ligand
system.
Within
inner
plexiform
layer
(IPL),
FLRT2
is
expressed
by
direction-selective
(DS)
circuit
neurons,
whereas
UNC5C/D
are
non-DS
projecting
to
adjacent
IPL
sublayers.
In
vivo
gain-
and
loss-of-function
experiments
demonstrate
binding
eliminates
growing
DS
dendrites
have
strayed
from
Abrogation
allows
mistargeted
arbors
persist,
elaborate,
acquire
synapses
partners.
Conversely,
UNC5C
misexpression
within
sublayers
inhibits
dendrite
growth
drives
into
Mechanistically,
UNC5s
promote
elimination
interfering
FLRT2-mediated
adhesion.
Based
on
their
broad
expression,
FLRT-UNC5
poised
exert
widespread
effects
upon
partner
choices
across
Cell Reports,
Journal Year:
2022,
Volume and Issue:
38(2), P. 110225 - 110225
Published: Jan. 1, 2022
In
mice,
retinal
direction
selectivity
is
organized
in
a
map
that
aligns
to
the
body
and
gravitational
axes
of
optic
flow,
little
known
about
how
this
develops.
We
find
maps
are
largely
present
at
eye
opening
develop
normally
absence
visual
experience.
Remarkably,
mice
lacking
beta2
subunit
neuronal
nicotinic
acetylcholine
receptors
(β2-nAChR-KO),
which
exhibit
drastically
reduced
cholinergic
waves
first
postnatal
week,
horizontal
motion
absent
while
vertical
remains.
tested
several
possible
mechanisms
could
explain
loss
β2-nAChR-KO
(wave
propagation
bias,
FRMD7
expression,
starburst
amacrine
cell
morphology),
but
all
were
found
be
intact
when
compared
with
WT
mice.
This
work
establishes
role
for
development
asymmetric
circuitry
mediates
via
an
unknown
mechanism.
Cell Reports,
Journal Year:
2023,
Volume and Issue:
42(5), P. 112476 - 112476
Published: May 1, 2023
The
wiring
of
visual
circuits
requires
that
retinal
neurons
functionally
connect
to
specific
brain
targets,
a
process
involves
activity-dependent
signaling
between
axons
and
their
postsynaptic
targets.
Vision
loss
in
various
ophthalmological
neurological
diseases
is
caused
by
damage
the
connections
from
eye
brain.
How
targets
influence
ganglion
cell
(RGC)
axon
regeneration
functional
reconnection
with
remains
poorly
understood.
Here,
we
established
paradigm
which
enhancement
neural
activity
distal
optic
pathway,
where
target
reside,
promotes
RGC
reinnervation
leads
rescue
optomotor
function.
Furthermore,
selective
activation
retinorecipient
neuron
subsets
sufficient
promote
regeneration.
Our
findings
reveal
key
role
for
neuronal
repair
highlight
potential
restore
damaged
sensory
inputs
via
proper
stimulation.
Current Opinion in Neurobiology,
Journal Year:
2023,
Volume and Issue:
81, P. 102752 - 102752
Published: July 25, 2023
Understanding
the
formation
of
complex
nervous
system
hinges
on
decoding
mechanism
that
specifies
a
vast
array
neuronal
types,
each
endowed
with
unique
morphology,
physiology,
and
connectivity.
As
pivotal
step
towards
addressing
this
problem,
seminal
work
has
been
devoted
to
characterizing
distinct
types.
In
recent
years,
high-throughput,
single-cell
transcriptomic
methods
have
enabled
rapid
inventory
cell
types
in
various
regions
system,
retina
exhibiting
complete
molecular
characterization
across
many
vertebrate
species.
This
invaluable
resource
furnished
fresh
perspective
for
investigating
principles
cell-type
specification,
thereby
advancing
our
understanding
retinal
development.
Accordingly,
review
focuses
most
characterizations
cells,
particular
focus
amacrine
cells
ganglion
cells.
These
investigations
unearthed
new
insights
into
their
specification.
Knowledge-Based Systems,
Journal Year:
2024,
Volume and Issue:
295, P. 111816 - 111816
Published: April 18, 2024
In
recent
years,
convolutional
neural
networks
(CNNs)
have
dominated
the
field
of
computer
vision.
Compared
to
traditional
methods,
these
network
algorithms
exhibit
strong
biomimetic
performance
advantages
in
complex
visual
tasks
due
their
brain-like
structure.
However,
because
some
necessary
characteristics
are
ignored,
differ
greatly
from
computational
mechanisms
brain.
This
paper
starts
with
extracting
basic
features
such
as
motion
direction
information
brain
and
abstracts,
generalizes
models
a
novel
artificial
system
(AVS)
for
detecting
object
color
images
based
on
existing
relevant
neurophysiological
knowledge.
We
propose
mathematical
model
quantification
mechanism
each
component
neuron
that
generates
selectivity
using
dendritic
models,
spiking
concepts
knowledge
retinal
direction-selective
ganglion
cell
pathways.
The
experiment
is
one
million
instances
under
different
environments
noise-free,
static
dynamic
random
noise,
salt-and-pepper
Gaussion
light
changing.
comparison
4
famous
CNNs,
LeNet-5,
EfficientNetB0,
ResNet18,
RegNetX-200MF,
we
test
verify
AVS's
effectiveness,
efficiency
generalization
ability
well
other
including
high
biological
rationality,
learning-free
capability,
interpretability
ease-of-use
etc.
AVS
demonstrates
neuroscience
still
has
important
implications
guiding
promoting
development
intelligence
technology.
Furthermore,
firstly
provides
successful
quantitative
reference
case
study
further
understanding
primary
cortical
encoding
Mathematics,
Journal Year:
2022,
Volume and Issue:
10(16), P. 2975 - 2975
Published: Aug. 17, 2022
How
specific
features
of
the
environment
are
represented
in
mammalian
brain
is
an
important
unexplained
mystery
neuroscience.
Visual
information
considered
to
be
captured
most
preferentially
by
brain.
As
one
visual
elements,
motion
direction
receptive
field
thought
collected
already
at
retinal
direction-selective
ganglion
cell
(DSGC)
layer.
However,
knowledge
(DS)
mechanisms
retina
has
remained
only
a
cellular
level,
and
there
lack
complete
direction-sensitivity
understanding
system.
Previous
studies
DS
models
have
been
limited
stage
one-dimensional
black-and-white
(binary)
images
or
still
biological
rationality.
In
this
paper,
we
innovatively
propose
two-dimensional,
eight-directional
detection
mechanism
for
grayscale
called
artificial
system
(AVS).
The
structure
neuronal
functions
highly
faithful
neuroscientific
perceptions
pathway,
thus
biologically
reasonable.
particular,
introducing
horizontal
contact
pathway
provided
cells
(HCs)
inner
nuclear
layer
forming
functional
collaboration
with
bipolar
(BCs),
limitation
that
previous
can
recognize
object
directions
binary
overcome;
proposed
model
solve
recognizing
problem
images.
Through
computer
simulation
experiments,
verified
AVS
effective
high
accuracy,
it
not
affected
shape,
size,
location
objects
field.
Its
excellent
noise
immunity
was
also
adding
multiple
types
experimental
data
set.
Compared
classical
convolutional
neural
network
(CNN),
completely
significantly
better
terms
effectiveness
immunity,
various
advantages
such
as
interpretability,
no
need
learning,
easy
hardware
implementation.
addition,
activation
characteristics
neurons
consistent
those
real
strong
neurofunctional
similarity
brain-like
superiority.
Moreover,
will
provide
novel
perspective
approach
analyzing
well
principles
face
cognitive
bottleneck
on
persisted
nearly
60
years.
Journal of Neuroscience,
Journal Year:
2024,
Volume and Issue:
unknown, P. e1461232024 - e1461232024
Published: March 21, 2024
An
organizational
feature
of
neural
circuits
is
the
specificity
synaptic
connections.
A
striking
example
direction-selective
(DS)
circuit
retina.
There
are
multiple
subtypes
DS
retinal
ganglion
cells
(DSGCs)
that
prefer
motion
along
one
four
preferred
directions.
This
computation
mediated
by
selective
wiring
a
single
inhibitory
interneuron,
starburst
amacrine
cell
(SAC),
with
each
DSGC
subtype
preferentially
receiving
input
from
subset
SAC
processes.
We
hypothesize
molecular
basis
this
in
part
unique
expression
profiles
subtypes.
To
test
this,
we
first
performed
paired
recordings
isolated
mouse
retinas
both
sexes
to
determine
postnatal
day
10
(P10)
represents
age
at
which
asymmetric
synapses
form.
Second,
RNA
sequencing
and
differential
analysis
on
P10
ON-OFF
DSGCs
tuned
for
either
nasal
or
ventral
identified
candidates
may
promote
direction-specific
wiring.
then
used
conditional
knock-out
strategy
role
candidate,
secreted
organizer
cerebellin-4
(Cbln4),
development
tuning.
Using
two-photon
calcium
imaging,
observed
small
deficit
directional
tuning
among
ventral-preferring
lacking
Cbln4,
though
whole-cell
voltage-clamp
did
not
identify
significant
change
inputs.
suggests
Cbln4
does
function
primarily
via
cell-autonomous
mechanism
instruct
circuits.
Nevertheless,
our
transcriptomic
candidate
factors
gaining
insights
into
mechanisms
circuit.
Annual Review of Vision Science,
Journal Year:
2024,
Volume and Issue:
10(1), P. 377 - 402
Published: Sept. 15, 2024
Synapse
formation
within
the
retinal
circuit
ensures
that
distinct
neuronal
types
can
communicate
efficiently
to
process
visual
signals.
Synapses
thus
form
core
of
computations
performed
by
circuit.
Retinal
synapses
are
diverse
but
be
broadly
categorized
into
multipartner
ribbon
and
1:1
conventional
synapses.
In
this
article,
we
review
our
current
understanding
cellular
molecular
mechanisms
regulate
functional
establishment
mammalian
synapses,
including
role
adhesion
proteins,
synaptic
extracellular
matrix
cytoskeletal-associated
activity-dependent
cues.
We
outline
future
directions
areas
research
will
expand
knowledge
these
mechanisms.
Understanding
regulators
moderating
synapse
function
not
only
reveals
integrated
developmental
processes
establish
circuits,
also
divulges
identity
could
engaged
during
disease
degeneration.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 17, 2024
Diverse
retinal
ganglion
cells
(RGCs)
transmit
distinct
visual
features
from
the
eye
to
brain.
Recent
studies
have
categorized
RGCs
into
45
types
in
mice
based
on
transcriptomic
profiles,
showing
strong
alignment
with
morphological
and
electrophysiological
properties.
However,
little
is
known
about
how
these
are
spatially
arranged
two-dimensional
surface-an
organization
that
influences
encoding-and
their
local
microenvironments
impact
development
neurodegenerative
responses.
To
address
this
gap,
we
optimized
a
workflow
combining
imaging-based
spatial
transcriptomics
(MERFISH)
immunohistochemical
co-staining
thin
flatmount
sections.
We
used
computational
methods
register
en
face
somata
distributions
of
all
molecularly
defined
RGC
types.
More
than
75%
(34/45)
exhibited
non-uniform
distributions,
likely
reflecting
adaptations
retina's
anatomy
animal's
environment.
By
analyzing
neighborhoods
each
cell,
identified
perivascular
located
near
blood
vessels.
Seven
enriched
niche,
including
members
intrinsically
photosensitive
(ipRGC)
direction-selective
(DSGC)
subclasses.
Orthologous
human
counterparts
-
Melanopsin-enriched
ipRGCs
ON
DSGCs
were
also
proximal
vessels,
suggesting
perivascularity
may
be
evolutionarily
conserved.
Following
optic
nerve
crush
mice,
M1-ipRGCs
showed
preferential
survival,
proximity
vessels
render
cell-extrinsic
neuroprotection
through
an
mTOR-independent
mechanism.
Overall,
our
work
offers
resource
characterizing
profiles
types,
enabling
future
development,
physiology,
neurodegeneration
at
individual
neuron
type
resolution
across
space.