Frontiers in Neural Circuits,
Journal Year:
2023,
Volume and Issue:
17
Published: Aug. 30, 2023
Despite
the
importance
of
postsynaptic
inhibitory
circuitry
targeted
by
mid/long-range
projections
(e.g.,
top-down
projections)
in
cognitive
functions,
its
anatomical
properties,
such
as
laminar
profile
and
neuron
type,
are
poorly
understood
owing
to
lack
efficient
tracing
methods.
To
this
end,
we
developed
a
method
that
combines
conventional
adeno-associated
virus
(AAV)-mediated
transsynaptic
with
distal-less
homeobox
(Dlx)
enhancer-restricted
expression
system
label
neurons.
We
called
"Dlx
Interneuron-SpECific
Tracing"
(DISECT).
applied
DISECT
corticocortical
circuit
from
secondary
motor
cortex
(M2)
primary
somatosensory
(S1)
wild-type
mice.
First,
injected
AAV1-Cre
into
M2,
which
enabled
Cre
recombinase
M2-input
recipient
S1
Second,
AAV1-hDlx-flex-green
fluorescent
protein
(GFP)
transduce
GFP
neurons
Cre-dependent
manner.
succeeded
exclusively
labeling
S1.
Laminar
analysis
labeled
via
indicated
were
distributed
superficial
deep
layers
This
distribution
was
aligned
density
axons
projecting
M2.
further
classified
types
using
immunohistochemistry
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 23, 2024
Behavioral
states
such
as
sleep
and
wake
are
highly
correlated
with
specific
patterns
of
rhythmic
activity
in
the
cortex.
During
low
arousal
slow
wave
sleep,
cortex
is
synchronized
dominated
by
frequency
rhythms
coordinated
across
multiple
regions.
Although
recent
evidence
suggests
that
GABAergic
inhibitory
neurons
key
players
cortical
state
modulation,
The
last
few
years
have
seen
an
explosion
in
the
number
of
tools
available
to
measure
neuronal
activity
using
fluorescence
imaging
(Chen
et
al.,
2013;
Feng
2019;
Jing
Sun
2018;
Wan
2021).
When
performed
vivo,
these
measurements
are
invariably
contaminated
by
hemodynamic
occlusion
artifacts.
In
widefield
calcium
imaging,
this
problem
is
well
recognized.
For
two-photon
however,
effects
only
been
sparsely
characterized.
Here
we
perform
a
quantification
changes
observed
with
GFP
expression
both
and
imaging.
We
find
that
many
instances
magnitude
signal
attributable
comparable
sensors.
Moreover,
were
spatially
heterogeneous,
over
cortical
regions
across
depth,
exhibited
complex
relationship
behavior.
Thus,
important
caveat
consider
when
analyzing
interpreting
not
just
but
also
data.
The
last
few
years
have
seen
an
explosion
in
the
number
of
tools
available
to
measure
neuronal
activity
using
fluorescence
imaging
(Chen
et
al.,
2013;
Feng
2019;
Jing
Sun
2018;
Wan
2021).
When
performed
vivo,
these
measurements
are
invariably
contaminated
by
hemodynamic
occlusion
artifacts.
In
widefield
calcium
imaging,
this
problem
is
well
recognized.
For
two-photon
however,
effects
only
been
sparsely
characterized.
Here
we
perform
a
quantification
changes
observed
with
GFP
expression
both
and
imaging.
We
find
that
many
instances
magnitude
signal
attributable
comparable
sensors.
Moreover,
were
spatially
heterogeneous,
over
cortical
regions
across
depth,
exhibited
complex
relationship
behavior.
Thus,
important
caveat
consider
when
analyzing
interpreting
not
just
but
also
data.
The
last
few
years
have
seen
an
explosion
in
the
number
of
tools
available
to
measure
neuronal
activity
using
fluorescence
imaging
(Chen
et
al.,
2013;
Feng
2019;
Jing
Sun
2018;
Wan
2021).
When
performed
vivo,
these
measurements
are
invariably
contaminated
by
hemodynamic
occlusion
artifacts.
In
widefield
calcium
imaging,
this
problem
is
well
recognized.
For
two-photon
however,
effects
only
been
sparsely
characterized.
Here
we
perform
a
quantification
changes
observed
with
GFP
expression
both
and
imaging.
We
find
that
many
instances
magnitude
signal
attributable
comparable
sensors.
Moreover,
were
spatially
heterogeneous,
over
cortical
regions
across
depth,
exhibited
complex
relationship
behavior.
Thus,
important
caveat
consider
when
analyzing
interpreting
not
just
but
also
data.
It
is
unknown
how
the
brain
orchestrates
coordination
of
global
neural
and
vascular
dynamics.
We
sought
to
uncover
role
a
sparse
but
unusual
population
genetically-distinct
interneurons
known
as
type-I
nNOS
neurons,
using
novel
pharmacological
strategic
unilaterally
ablate
these
neurons
from
somatosensory
cortex
mice.
Region-specific
ablation
produced
changes
in
both
activity
dynamics,
decreased
power
delta-band
local
field
potential,
reduced
sustained
responses
prolonged
sensory
stimulation,
abolished
post-stimulus
undershoot
cerebral
blood
volume.
Coherence
between
left
right
gamma-band
envelope
volume
at
ultra-low
frequencies
was
decreased,
suggesting
type-1
integrate
long-range
signals.
Lastly,
we
observed
decreases
amplitude
resting-state
oscillations
vasomotion
following
neurons.
This
demonstrates
that
small
nNOS-positive
are
indispensable
for
regulating
dynamics
whole
implicates
disruption
diseases
ranging
neurodegeneration
sleep
disturbances.
It
is
unknown
how
the
brain
orchestrates
coordination
of
global
neural
and
vascular
dynamics.
We
sought
to
uncover
role
a
sparse
but
unusual
population
genetically-distinct
interneurons
known
as
type-I
nNOS
neurons,
using
novel
pharmacological
strategic
unilaterally
ablate
these
neurons
from
somatosensory
cortex
mice.
Region-specific
ablation
produced
changes
in
both
activity
dynamics,
decreased
power
delta-band
local
field
potential,
reduced
sustained
responses
prolonged
sensory
stimulation,
abolished
post-stimulus
undershoot
cerebral
blood
volume.
Coherence
between
left
right
gamma-band
envelope
volume
at
ultra-low
frequencies
was
decreased,
suggesting
type-1
integrate
long-range
signals.
Lastly,
we
observed
decreases
amplitude
resting-state
oscillations
vasomotion
following
neurons.
This
demonstrates
that
small
nNOS-positive
are
indispensable
for
regulating
dynamics
whole
implicates
disruption
diseases
ranging
neurodegeneration
sleep
disturbances.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 16, 2024
Abstract
Neuronal
regulation
of
cerebrovasculature
underlies
brain
imaging
techniques
reliant
on
cerebral
blood
flow
(CBF)
changes.
However,
interpreting
these
signals
requires
understanding
their
neural
correlates.
Parvalbumin
(PV)
interneurons
are
crucial
in
network
activity,
but
impact
CBF
is
not
fully
understood.
Optogenetic
studies
show
that
stimulating
cortical
PV
induces
diverse
responses,
including
rapid
increases,
decreases,
and
slower
delayed
increases.
To
clarify
this
relationship,
we
measured
hemodynamic
responses
to
optogenetic
stimulation
expressing
Channelrhodopsin-2
during
evoked
ongoing
resting-state
activity
the
somatosensory
cortex
awake
mice.
Two-photon
microscopy
(2P)
Ca2+
showed
robust
activation
PV-positive
(PV+)
cells
inhibition
PV-negative
(PV-)
cells.
Prolonged
PV+
cell
led
a
delayed,
slow
increase,
resembling
secondary
peak
response
whisker
stimulation.
2P
vessel
diameter
measurements
revealed
induced
arterial
vasodilation
superficial
layers
deeper
layers.
Ongoing
recordings
indicated
both
PV-cell
populations
modulate
fluctuations
at
rest,
with
having
greater
impact.
These
findings
generate
complex
depth-dependent
vascular
response,
dominated
by
changes
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 29, 2024
ABSTRACT
The
last
few
years
have
seen
an
explosion
in
the
number
of
tools
available
to
measure
neuronal
activity
using
fluorescence
imaging
(Chen
et
al.,
2013;
Feng
2019;
Jing
Sun
2018;
Wan
2021).
When
performed
vivo,
these
measurements
are
invariably
contaminated
by
hemodynamic
occlusion
artifacts.
In
widefield
calcium
imaging,
this
problem
is
well
recognized.
For
two-photon
however,
effects
only
been
sparsely
characterized.
Here
we
perform
a
quantification
changes
observed
with
GFP
expression
both
and
imaging.
We
find
that
many
instances
magnitude
signal
attributable
comparable
sensors.
Moreover,
were
spatially
heterogeneous,
over
cortical
regions
across
depth,
exhibited
complex
relationship
behavior.
Thus,
important
caveat
consider
when
analyzing
interpreting
not
just
but
also
data.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 4, 2024
Abstract
Somatostatin-expressing
(SST)
interneurons
modulate
hemodynamic
responses
both
directly
and
indirectly,
but
their
precise
role
remains
unclear.
Here,
we
investigated
how
SST
affect
hemodynamics
using
a
combination
of
electrophysiology,
intrinsic
optical
imaging,
calcium
fMRI
with
pharmacological,
optogenetic,
chemogenetic
manipulations.
Prolonged
optogenetic
stimulation
neurons
induces
fast
vasodilation
through
nitric
oxide
synthase-expressing
that
co-express
SST,
slow
mediated
by
astrocytes.
Pharmacological
blocking
receptors
suppresses
astrocyte
activity
delayed
vasodilation,
while
early
unchanged.
Similar
neurovascular
coupling
mechanisms
are
observed
during
prolonged
sensory
stimulation,
which
also
vasodilation.
The
the
SST-astrocyte
pathway,
enhances
specificity
cerebral
blood
volume-weighted
signals
to
cortical
layer
4,
as
confirmed
inhibition
neurons.
Our
findings
suggest
neuron-astrocyte-vascular
pathway
shapes
is
critical
for
achieving
high-specificity,
laminar-resolution
fMRI,
increasingly
pursued
in
human
cognitive
studies.