Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Дек. 19, 2022
Abstract
Acutely
silencing
specific
neurons
informs
about
their
functional
roles
in
circuits
and
behavior.
Existing
optogenetic
silencers
include
ion
pumps,
channels,
metabotropic
receptors,
tools
that
damage
the
neurotransmitter
release
machinery.
While
former
hyperpolarize
cell,
alter
ionic
gradients
or
cellular
biochemistry,
latter
allow
only
slow
recovery,
requiring
de
novo
synthesis.
Thus,
combining
fast
activation
reversibility
are
needed.
Here,
we
use
light-evoked
homo-oligomerization
of
cryptochrome
CRY2
to
silence
synaptic
transmission,
by
clustering
vesicles
(SVs).
We
benchmark
this
tool,
optoSynC,
Caenorhabditis
elegans
,
zebrafish,
murine
hippocampal
neurons.
optoSynC
clusters
SVs,
observable
electron
microscopy.
Locomotion
occurs
with
tau
on
~7.2
s
recovers
off
~6.5
min
after
light-off.
can
inhibit
exocytosis
for
several
hours,
at
very
low
light
intensities,
does
not
affect
currents,
biochemistry
proteins,
may
further
manipulating
different
SV
pools
transfer
SVs
between
them.
Nature Methods,
Год журнала:
2024,
Номер
21(7), С. 1275 - 1287
Опубликована: Май 29, 2024
Abstract
Information
is
transmitted
between
brain
regions
through
the
release
of
neurotransmitters
from
long-range
projecting
axons.
Understanding
how
activity
such
connections
contributes
to
behavior
requires
efficient
methods
for
reversibly
manipulating
their
function.
Chemogenetic
and
optogenetic
tools,
acting
endogenous
G-protein-coupled
receptor
pathways,
can
be
used
modulate
synaptic
transmission,
but
existing
tools
are
limited
in
sensitivity,
spatiotemporal
precision
or
spectral
multiplexing
capabilities.
Here
we
systematically
evaluated
multiple
bistable
opsins
applications
found
that
Platynereis
dumerilii
ciliary
opsin
(
Pd
CO)
an
efficient,
versatile,
light-activated
suppress
transmission
mammalian
neurons
with
high
temporal
vivo.
CO
has
useful
biophysical
properties
enable
other
actuators
reporters.
We
demonstrate
conduct
reversible
loss-of-function
experiments
projections
behaving
animals,
thereby
enabling
detailed
synapse-specific
functional
circuit
mapping.
To
determine
how
neuronal
circuits
encode
and
drive
behavior,
it
is
often
necessary
to
measure
manipulate
different
aspects
of
neurochemical
signaling
in
awake
animals.
Optogenetics
calcium
sensors
have
paved
the
way
for
these
types
studies,
allowing
perturbation
readout
spiking
activity
within
genetically
defined
cell
types.
However,
methods
lack
ability
further
disentangle
roles
individual
neuromodulator
neuropeptides
on
behavior.
We
review
recent
advances
chemical
biology
tools
that
enable
precise
spatiotemporal
monitoring
control
over
neuroeffectors
their
receptors
vivo.
also
highlight
discoveries
enabled
by
such
tools,
revealing
molecules
signal
across
timescales
learning,
orchestrate
behavioral
changes,
modulate
circuit
activity.
Journal of Cell Science,
Год журнала:
2021,
Номер
134(22)
Опубликована: Ноя. 15, 2021
Rhodopsins
are
photoreceptive
membrane
proteins
consisting
of
a
common
heptahelical
transmembrane
architecture
that
contains
retinal
chromophore.
Rhodopsin
was
first
discovered
in
the
animal
retina
1876,
but
different
type
rhodopsin,
bacteriorhodopsin,
reported
to
be
present
cell
an
extreme
halophilic
archaeon,
Halobacterium
salinarum,
95
years
later.
Although
these
findings
were
made
by
physiological
observation
pigmented
tissue
and
bodies,
recent
progress
genomic
metagenomic
analyses
has
revealed
there
more
than
10,000
microbial
rhodopsins
9000
with
large
diversity
tremendous
new
functionality.
In
this
Cell
Science
at
Glance
article
accompanying
poster,
we
provide
overview
functions,
structures,
color
discrimination
mechanisms
optogenetic
applications
two
rhodopsin
families,
will
also
highlight
third
distinctive
family,
heliorhodopsin.
The Journal of Physiology,
Год журнала:
2022,
Номер
600(9), С. 2049 - 2075
Опубликована: Март 16, 2022
Abstract
Twenty‐five
years
ago,
a
new
physiological
preparation
called
the
working
heart–brainstem
(WHBP)
was
introduced
with
claim
it
would
provide
platform
allowing
studies
not
possible
before
in
cardiovascular,
neuroendocrine,
autonomic
and
respiratory
research.
Herein,
we
review
some
of
progress
made
WHBP,
advantages
disadvantages
along
potential
future
applications,
photographs
technical
drawings
all
customised
equipment
used
for
preparation.
Using
mice
or
rats,
WHBP
is
an
situ
experimental
model
that
perfused
via
extracorporeal
circuit
benefitting
from
unprecedented
surgical
access,
mechanical
stability
brain
whole
cell
recording
uncompromised
use
pharmacological
agents
akin
to
vitro
approaches.
The
has
revealed
novel
mechanistic
insights
into,
example,
generation
distinct
rhythms,
neurogenesis
sympathetic
activity,
coupling
between
respiration
heart
circulation,
hypothalamic
spinal
control
mechanisms,
peripheral
central
chemoreceptor
mechanisms.
Insights
have
been
gleaned
into
diseases
such
as
hypertension,
failure
sleep
apnoea.
Findings
ratified
conscious
vivo
animals
when
tested
translated
humans.
We
conclude
by
discussing
applications
including
two‐photon
imaging
nervous
systems
adoption
pharmacogenetic
tools
will
improve
our
understanding
mechanisms
reveal
may
guide
treatment
strategies
cardiorespiratory
diseases.
image
ACS Nano,
Год журнала:
2022,
Номер
17(1), С. 561 - 574
Опубликована: Дек. 22, 2022
Neurotransmitters
and
neuromodulators
mediate
communication
between
neurons
other
cell
types;
knowledge
of
release
dynamics
is
critical
to
understanding
their
physiological
role
in
normal
pathological
brain
function.
Investigation
into
transient
neurotransmitter
has
largely
been
hindered
due
electrical
material
requirements
for
electrochemical
stimulation
recording.
Current
systems
require
complex
electronics
biasing
amplification
rely
on
materials
that
offer
limited
sensor
selectivity
sensitivity.
These
restrictions
result
bulky,
tethered,
or
battery-powered
impacting
behavior
constant
care
subjects.
To
overcome
these
challenges,
we
demonstrate
a
fully
implantable,
wireless,
battery-free
platform
enables
optogenetic
recording
catecholamine
real
time.
The
device
nearly
1/10th
the
size
previously
reported
examples
includes
probe
relies
multilayer
electrode
architecture
featuring
microscale
light
emitting
diode
(μ-LED)
carbon
nanotube
(CNT)-based
with
sensitivities
among
highest
recorded
literature
(1264.1
nA
μM
Neurophotonics
was
launched
in
2014
coinciding
with
the
launch
of
BRAIN
Initiative
focused
on
development
technologies
for
advancement
neuroscience.
For
last
seven
years,
Neurophotonics'
agenda
has
been
well
aligned
this
focus
neurotechnologies
featuring
new
optical
methods
and
tools
applicable
to
brain
studies.
While
2.0
is
pivoting
towards
applications
these
novel
quest
understand
brain,
article
we
review
an
extensive
diverse
toolkit
explore
function
that
have
emerged
from
related
large-scale
efforts
measurement
manipulation
structure
function.
Here,
neurophotonic
mostly
animal
A
companion
article,
scheduled
appear
later
year,
will
cover
diffuse
imaging
noninvasive
human
each
domain,
outline
current
state-of-the-art
respective
technologies,
identify
areas
where
innovation
needed
provide
outlook
future
directions.
Abstract
Controlling
chemical
processes
in
live
cells
is
a
challenging
task.
The
spatial
heterogeneity
of
biochemical
reactions
often
overlooked
by
conventional
means
incubating
with
desired
chemicals.
A
comprehensive
understanding
spatially
diverse
requires
precise
control
over
molecular
activities
at
the
subcellular
level.
Herein,
closed‐loop
optoelectronic
system
developed
that
allows
manipulation
biomolecular
high
spatiotemporal
precision.
Chemical‐selective
fluorescence
signals
are
utilized
to
command
lasers
trigger
specific
or
activation
photoswitchable
inhibitors
targets.
This
technology
fully
compatible
laser
scanning
confocal
microscopes.
authors
demonstrate
selective
interactions
405
nm
targeted
organelles
and
simultaneous
monitoring
cell
responses
fluorescent
protein
signals.
Notably,
blue
interaction
endoplasmic
reticulum
leads
more
pronounced
reduction
cytosolic
green
comparison
nuclei
lipid
droplets.
Moreover,
when
combined
inhibitor,
microtubule
polymerization
selectively
inhibited
within
compartments.
enables
optical
drug
activities,
exclusively
targets,
while
minimizing
undesired
effects
on
non‐targeted
locations.
Ciliary
opsins
(c-opsin)
have
been
identified
not
only
in
vertebrates
but
also
invertebrates.
An
invertebrate
ciliary
opsin
was
recently
the
fan
worm
Acromegalomma
interruptum
(formerly
named
Megalomma
interrupta);
however,
its
spectral
and
signaling
characteristics
are
unknown.
In
present
study,
we
characterized
properties
light-induced
cellular
of
(Acromegalomma
(AcrInvC-opsin)).
AcrInvC-opsin
showed
an
absorption
maximum
at
464
nm,
upon
blue
light
absorption,
spectrum
red-shifted
by
approximately
50
nm.
The
two
states
interconvertible
illumination
with
orange
light.
Blue
caused
specific
coupling
Gi,
sustained
Gi
dissociation,
decreased
intracellular
cAMP
levels,
activation
GIRK
channels.
responses
activated
were
partially
terminated
illumination.
These
light-dependent
indicate
that
InvC-opsin
is
a
typical
bistable
pigment
wherein
resting
can
be
interconverted
visible
We
attempted
to
modulate
functional
using
site-directed
mutagenesis.
Substitution
Ser-94
Ala
little
shift
state
further
red
∼10
nm
state,
indicating
spectra
tuned
differently.
contrast,
substitution
S94A
did
significantly
affect
AcrInvC-opsin.
Because
blue-sensitive,
Gi/o-biased,
pigment,
it
has
potential
serve
as
optical
control
tool
specifically
reversibly
regulate
Gi/o-dependent
pathways