Neuropeptide‐Dependent Spike Time Precision and Plasticity in Circadian Output Neurons
European Journal of Neuroscience,
Journal Year:
2025,
Volume and Issue:
61(5)
Published: March 1, 2025
ABSTRACT
Circadian
rhythms
influence
various
physiological
and
behavioral
processes
such
as
sleep–wake
cycles,
hormone
secretion,
metabolism.
In
Drosophila
,
an
important
set
of
circadian
output
neurons
is
called
pars
intercerebralis
(PI)
neurons,
which
receive
input
from
specific
clock
DN1.
These
DN1
can
further
be
subdivided
into
functionally
anatomically
distinctive
anterior
(DN1a)
posterior
(DN1p)
clusters.
The
neuropeptide
diuretic
hormones
31
(Dh31)
44
(Dh44)
are
the
insect
neuropeptides
known
to
activate
PI
control
activity
rhythms.
However,
neurophysiological
basis
how
Dh31
Dh44
affect
neural
coding
mechanisms
underlying
sleep
in
not
well
understood.
Here,
we
identify
Dh31/Dh44‐dependent
spike
time
precision
plasticity
neurons.
We
first
find
that
a
mixture
enhanced
firing
compared
application
alone
alone.
next
synthesized
affects
membrane
potential
dynamics
precise
timing
neuronal
through
their
synergistic
interaction,
possibly
mediated
by
calcium‐activated
potassium
channel
conductance.
Further,
characterize
Dh31/Dh44
enhances
postsynaptic
potentials
Together,
these
results
suggest
multiplexed
neuropeptide‐dependent
.
Language: Английский
Neuropeptide-dependent spike time precision and plasticity in circadian output neurons
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 7, 2024
Abstract
Circadian
rhythms
influence
various
physiological
and
behavioral
processes
such
as
sleep-wake
cycles,
hormone
secretion,
metabolism.
output
neurons
are
a
group
of
that
receive
input
from
the
central
circadian
clock
located
in
suprachiasmatic
nucleus
mammalian
brain
transmit
timing
information
to
different
regions
body,
coordinating
processes.
In
Drosophila
,
an
important
set
called
pars
intercerebralis
(PI)
neurons,
which
specific
DN1.
These
can
further
be
subdivided
into
functionally
anatomically
distinctive
anterior
(DN1a)
posterior
(DN1p)
clusters.
The
neuropeptide
diuretic
hormones
31
(Dh31)
44
(Dh44)
insect
neuropeptides
known
activate
PI
control
activity
rhythms.
However,
neurophysiological
basis
how
Dh31
Dh44
affect
neural
coding
mechanisms
underlying
sleep
is
not
well
understood.
Here,
we
identify
Dh31/Dh44-dependent
spike
time
precision
plasticity
neurons.
We
find
application
synthesized
affects
membrane
potential
dynamics
precise
neuronal
firing
through
their
synergistic
interaction,
possibly
mediated
by
calcium-activated
potassium
channel
conductance.
Further,
characterize
Dh31/Dh44
enhances
postsynaptic
potentials
Together,
these
results
suggest
multiplexed
neuropeptide-dependent
.
Language: Английский
Clinical and genetic characterization of a progressive RBL2-associated neurodevelopmental disorder
Brain,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 18, 2024
Abstract
Retinoblastoma
(RB)
proteins
are
highly
conserved
transcriptional
regulators
that
play
important
roles
during
development
by
regulating
cell-cycle
gene
expression.
RBL2
dysfunction
has
been
linked
to
a
severe
neurodevelopmental
disorder.
However,
date,
clinical
features
have
only
described
in
six
individuals
carrying
five
biallelic
predicted
loss
of
function
(pLOF)
variants.
To
define
the
phenotypic
effects
mutations
detail,
we
identified
and
clinically
characterized
cohort
35
patients
from
20
families
pLOF
variants
RBL2,
including
fifteen
new
substantially
broaden
molecular
spectrum.
The
presentation
affected
is
range
neurological
developmental
abnormalities.
Global
delay
intellectual
disability
were
uniformly
observed,
ranging
moderate
profound
involving
lack
acquisition
key
motor
speech
milestones
most
patients.
Disrupted
sleep
was
also
evident
some
Frequent
included
postnatal
microcephaly,
infantile
hypotonia,
aggressive
behaviour,
stereotypic
movements,
seizures,
non-specific
dysmorphic
features.
Neuroimaging
cerebral
atrophy,
white
matter
volume
loss,
corpus
callosum
hypoplasia
cerebellar
atrophy.
In
parallel,
used
fruit
fly,
Drosophila
melanogaster,
investigate
how
disruption
orthologue
Rbf
impacts
nervous
system
development.
We
found
LOF
mutants
recapitulate
several
harbouring
variants,
delay,
alterations
head
brain
morphology,
locomotor
defects,
perturbed
sleep.
Surprisingly,
addition
its
known
role
controlling
tissue
growth
development,
continued
expression
required
fully
differentiated
post-mitotic
neurons
for
normal
locomotion
Drosophila,
adult-stage
neuronal
re-expression
sufficient
rescue
mutant
defects.
Taken
together,
our
study
provides
experimental
basis
understand
genotype-phenotype
correlations
an
RBL2-linked
disorder,
suggests
restoring
through
therapy
approaches
may
ameliorate
symptoms
caused
pLOF.
Language: Английский