Detecting
rapid,
coincident
changes
across
sensory
modalities
is
essential
for
recognition
of
sudden
threats
or
events.
Using
two-photon
calcium
imaging
in
identified
cell
types
awake,
head-fixed
mice,
we
show
that,
among
the
basic
features
a
sound
envelope,
loud
onsets
are
dominant
feature
coded
by
auditory
cortex
neurons
projecting
to
primary
visual
(V1).
In
V1,
small
number
layer
1
interneurons
gates
this
cross-modal
information
flow
context-dependent
manner.
dark
conditions,
inputs
lead
suppression
V1
population.
However,
when
input
coincides
with
stimulus,
responses
boosted
most
strongly
after
onsets.
Thus,
dynamic,
asymmetric
circuit
connecting
AC
and
contributes
encoding
events
that
sounds.
Fluorescent
calcium
indicators
are
often
used
to
investigate
neural
dynamics,
but
the
relationship
between
fluorescence
and
action
potentials
(APs)
remains
unclear.
Most
APs
can
be
detected
when
soma
almost
fills
microscope's
field
of
view,
image
populations
neurons,
necessitating
a
large
generating
fewer
photons
per
neuron,
compromising
AP
detection.
Here,
we
characterized
AP-fluorescence
transfer
function
in
vivo
for
48
layer
2/3
pyramidal
neurons
primary
visual
cortex,
with
simultaneous
imaging
cell-attached
recordings
from
transgenic
mice
expressing
GCaMP6s
or
GCaMP6f.
While
most
were
under
optimal
conditions,
conditions
typical
population
studies,
only
minority
1
2
events
(often
<10%
~20-30%,
respectively),
emphasizing
limits
detection
more
realistic
conditions.Neurons,
cells
that
make
up
nervous
system,
transmit
information
using
electrical
signals
known
as
spikes.
Studying
spiking
patterns
brain
is
essential
understand
perception,
memory,
thought,
behaviour.
One
way
do
by
recording
activity
microelectrodes.
Another
study
neuronal
molecules
change
how
they
interact
light
binds
them,
since
changes
concentration
indicative
spiking.
That
observed
specialized
microscopes
know
two-photon
microscopes.
Using
indicators,
it
possible
simultaneously
record
hundreds
even
thousands
neurons.
However,
spikes
not
translate
one-to-one.
In
order
interpret
data,
important
associated
individual
The
directly
measure
this
same
neuron.
extremely
challenging
experimentally,
so
type
data
rare.
To
shed
some
on
this,
Huang,
Ledochowitsch
et
al.
had
been
genetically
modified
produce
indicator
cortex
obtained
both
measurements
these
These
experiments
revealed
that,
while
majority
time
periods
containing
multi-spike
could
identified
microscopy,
average,
less
than
10%
isolated
single
detectable.
This
an
caveat
researchers
need
take
into
consideration
interpreting
results.
findings
intended
serve
guide
studies
look
at
mammalian
level.
addition,
provided
will
useful
reference
development
sensors,
benchmark
improve
computational
approaches
detecting
predicting
PLoS Computational Biology,
Год журнала:
2020,
Номер
16(9), С. e1008198 - e1008198
Опубликована: Сен. 15, 2020
Calcium
imaging
with
fluorescent
protein
sensors
is
widely
used
to
record
activity
in
neuronal
populations.
The
transform
between
neural
and
calcium-related
fluorescence
involves
nonlinearities
low-pass
filtering,
but
the
effects
of
transformation
on
analyses
populations
are
not
well
understood.
We
compared
spikes
matched
behaving
mice.
report
multiple
discrepancies
performed
two
types
data,
including
changes
single-neuron
selectivity
population
decoding.
These
were
only
partially
resolved
by
spike
inference
algorithms
applied
fluorescence.
To
model
relation
spiking
we
simultaneously
recorded
from
individual
neurons.
Using
these
recordings
developed
a
transforming
trains
synthetic-imaging
data.
recapitulated
differences
analyses.
Our
analysis
highlights
challenges
relating
electrophysiology
suggests
forward
modeling
as
an
effective
way
understand
Nature,
Год журнала:
2022,
Номер
612(7939), С. 328 - 337
Опубликована: Ноя. 30, 2022
Abstract
The
precise
mechanisms
that
lead
to
cognitive
decline
in
Alzheimer’s
disease
are
unknown.
Here
we
identify
amyloid-plaque-associated
axonal
spheroids
as
prominent
contributors
neural
network
dysfunction.
Using
intravital
calcium
and
voltage
imaging,
show
a
mouse
model
of
demonstrates
severe
disruption
long-range
connectivity.
This
is
caused
by
action-potential
conduction
blockades
due
enlarging
acting
electric
current
sinks
size-dependent
manner.
Spheroid
growth
was
associated
with
an
age-dependent
accumulation
large
endolysosomal
vesicles
mechanistically
linked
Pld3
—a
potential
Alzheimer’s-disease-associated
risk
gene
1
encodes
lysosomal
protein
2,3
highly
enriched
spheroids.
Neuronal
overexpression
led
vesicle
spheroid
enlargement,
which
worsened
blockades.
By
contrast,
deletion
reduced
size,
leading
improved
electrical
function.
Thus,
targeted
modulation
biogenesis
neurons
could
potentially
reverse
spheroid-induced
circuit
abnormalities
disease,
independent
amyloid
removal.
Cell,
Год журнала:
2022,
Номер
185(18), С. 3408 - 3425.e29
Опубликована: Авг. 18, 2022
Genetically
encoded
voltage
indicators
are
emerging
tools
for
monitoring
dynamics
with
cell-type
specificity.
However,
current
enable
a
narrow
range
of
applications
due
to
poor
performance
under
two-photon
microscopy,
method
choice
deep-tissue
recording.
To
improve
indicators,
we
developed
multiparameter
high-throughput
platform
optimize
microscopy.
Using
this
system,
identified
JEDI-2P,
an
indicator
that
is
faster,
brighter,
and
more
sensitive
photostable
than
its
predecessors.
We
demonstrate
JEDI-2P
can
report
light-evoked
responses
in
axonal
termini
Drosophila
interneurons
the
dendrites
somata
amacrine
cells
isolated
mouse
retina.
also
optically
record
individual
cortical
neurons
awake
behaving
mice
30
min
using
both
resonant-scanning
ULoVE
random-access
Finally,
recording
robustly
detect
spikes
at
depths
exceeding
400
μm
correlations
pairs
neurons.
