The
sodium
leak
channel
(NALCN)
is
essential
for
survival
in
mammals:
NALCN
mutations
are
life-threatening
humans
and
knockout
lethal
mice.
However,
the
basic
functional
pharmacological
properties
of
have
remained
elusive.
Here,
we
found
that
robust
function
heterologous
systems
requires
co-expression
UNC79,
UNC80,
FAM155A.
resulting
complex
constitutively
active
conducts
monovalent
cations
but
blocked
by
physiological
concentrations
extracellular
divalent
cations.
Our
data
support
notion
directly
responsible
increased
excitability
observed
a
variety
neurons
reduced
Ca2+.
Despite
smaller
number
voltage-sensing
residues
NALCN,
constitutive
activity
modulated
voltage,
suggesting
domains
can
give
rise
to
broader
range
gating
phenotypes
than
previously
anticipated.
work
points
toward
formerly
unknown
contributions
neuronal
opens
avenues
targeting.
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Окт. 1, 2021
Abstract
Signals
from
the
central
circadian
pacemaker,
suprachiasmatic
nucleus
(SCN),
must
be
decoded
to
generate
daily
rhythms
in
hormone
release.
Here,
we
hypothesized
that
SCN
entrains
paraventricular
(PVN)
time
release
of
corticosterone.
In
vivo
recording
revealed
a
critical
circuit
vasoactive
intestinal
peptide
(SCN
VIP
)-producing
neurons
PVN
corticotropin-releasing
(PVN
CRH
neurons.
peak
clock
gene
expression
around
midday
and
calcium
activity
about
three
hours
later.
Loss
Bmal1
results
arrhythmic
dramatically
reduces
amplitude
precision
corticosterone
activation
(and
inactivation
increases)
activity,
by
inhibiting
We
conclude
depends
on
coordinated
neuronal
both
Proceedings of the National Academy of Sciences,
Год журнала:
2017,
Номер
114(41)
Опубликована: Сен. 26, 2017
Significance
Monitoring
neuronal
activity
in
freely
moving,
behaving
animals
is
a
holy
grail
of
neuroscience.
Here
we
present
noninvasive
tool
that
links
the
calcium
profiles
specific
fly
neurons
to
real-time
behavior.
Optogenetic
manipulation
two
groups
circadian
indicates
they
drive
sleep
or
locomotor
activity.
The
patterns
are
also
distinct
and
couple
well
sleep/activity
phases
sleep-promoting
appear
more
active
when
flies
initiate
daytime
sleep,
whereas
activity-promoting
fire
strongly
coincident
with
evening
peak.
This
new
approach
complementary
electrophysiological
recording
GCaMP
imaging,
especially
for
small
organisms
behavorial
paradigms
which
these
traditional
methods
not
practical.
Physiological Reviews,
Год журнала:
2020,
Номер
100(4), С. 1415 - 1454
Опубликована: Март 12, 2020
Animals
synchronize
to
the
environmental
day-night
cycle
by
means
of
an
internal
circadian
clock
in
brain.
In
mammals,
this
timekeeping
mechanism
is
housed
suprachiasmatic
nucleus
(SCN)
hypothalamus
and
entrained
light
input
from
retina.
One
output
SCN
a
neural
code
for
time,
which
arises
collective
activity
neurons
within
circuit
comprises
two
fundamental
components:
1)
periodic
alterations
spontaneous
excitability
individual
that
result
higher
firing
rates
during
day
lower
at
night,
2)
synchronization
these
cellular
oscillations
throughout
SCN.
review,
we
summarize
current
evidence
identity
ion
channels
mechanisms
they
set
rhythmic
parameters
time
code.
During
day,
voltage-dependent
independent
Na
+
Ca
2+
currents,
as
well
several
K
contribute
increased
membrane
therefore
frequency.
At
increase
different
including
-activated
BK
hyperpolarization
decreased
firing.
Layered
on
top
intrinsically
regulated
changes
excitability,
more
than
dozen
neuromodulators
influence
action
potential
rhythmicity
neurons,
facilitating
both
plasticity
The
sodium
leak
channel
(NALCN)
is
essential
for
survival
in
mammals:
NALCN
mutations
are
life-threatening
humans
and
knockout
lethal
mice.
However,
the
basic
functional
pharmacological
properties
of
have
remained
elusive.
Here,
we
found
that
robust
function
heterologous
systems
requires
co-expression
UNC79,
UNC80,
FAM155A.
resulting
complex
constitutively
active
conducts
monovalent
cations
but
blocked
by
physiological
concentrations
extracellular
divalent
cations.
Our
data
support
notion
directly
responsible
increased
excitability
observed
a
variety
neurons
reduced
Ca2+.
Despite
smaller
number
voltage-sensing
residues
NALCN,
constitutive
activity
modulated
voltage,
suggesting
domains
can
give
rise
to
broader
range
gating
phenotypes
than
previously
anticipated.
work
points
toward
formerly
unknown
contributions
neuronal
opens
avenues
targeting.
