Cell Reports Medicine,
Год журнала:
2024,
Номер
5(11), С. 101781 - 101781
Опубликована: Окт. 17, 2024
Confronting
oxytocin
and
vasopressin
deficits
in
autism
spectrum
disorders
rare
syndromes
brought
promises
disappointments
for
the
treatment
of
social
disabilities.
We
searched
downstream
targets
alleviating
a
mouse
model
Prader-Willi
syndrome
Schaaf-Yang
syndrome,
both
associated
with
high
prevalence
autism.
found
population
neurons
lateral
septum-activated
on
termination
contacts-which
inhibit
as
per
degree
peer
affiliation.
These
are
somatostatin
expressing
receptors
coupled
to
GABA-B
signaling,
which
inhibited
via
GABA-A
channels
by
vasopressin-excited
GABA
neurons.
Loss
or
signaling
recapitulated
disease
phenotype.
By
contrast,
deactivation
receptor
alleviated
models
increasing
duration
contacts
mates
strangers.
findings
provide
new
insights
into
framework
disabilities
neuropsychiatric
disorders.
Nature,
Год журнала:
2022,
Номер
613(7945), С. 696 - 703
Опубликована: Ноя. 30, 2022
Abstract
In
humans,
traumatic
social
experiences
can
contribute
to
psychiatric
disorders
1
.
It
is
suggested
that
trauma
impairs
brain
reward
function
such
behaviour
no
longer
rewarding,
leading
severe
avoidance
2,3
rodents,
the
chronic
defeat
stress
(CSDS)
model
has
been
used
understand
neurobiology
underlying
susceptibility
versus
resilience
following
trauma,
yet
little
known
regarding
its
impact
on
4,5
Here
we
show
that,
CSDS,
a
subset
of
male
and
female
mice,
termed
susceptible
(SUS),
avoid
interaction
with
non-aggressive,
same-sex
juvenile
C57BL/6J
mice
do
not
develop
context-dependent
encounters
them.
Non-social
stressors
have
effect
in
either
sex.
Next,
using
whole-brain
Fos
mapping,
vivo
Ca
2+
imaging
whole-cell
recordings,
identified
population
stress/threat-responsive
lateral
septum
neurotensin
(NT
LS
)
neurons
are
activated
by
interactions
only
SUS
but
resilient
or
unstressed
control
mice.
Optogenetic
chemogenetic
manipulation
NT
their
downstream
connections
modulates
reward.
Together,
these
data
suggest
previously
rewarding
targets
possibly
perceived
as
threats
resulting
from
hyperactive
occlude
processing.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Апрель 5, 2023
Major
depressive
disorder
ranks
as
a
major
burden
of
disease
worldwide,
yet
the
current
antidepressant
medications
are
limited
by
frequent
non-responsiveness
and
significant
side
effects.
The
lateral
septum
(LS)
is
thought
to
control
depression,
however,
cellular
circuit
substrates
largely
unknown.
Here,
we
identified
subpopulation
LS
GABAergic
adenosine
A
Frontiers in Systems Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Апрель 17, 2023
Anxiety
disorders
are
the
most
common
class
of
mental
illness
in
U.S.,
affecting
40
million
individuals
annually.
is
an
adaptive
response
to
a
stressful
or
unpredictable
life
event.
Though
evolutionarily
thought
aid
survival,
excess
intensity
duration
anxiogenic
can
lead
plethora
adverse
symptoms
and
cognitive
dysfunction.
A
wealth
data
has
implicated
medial
prefrontal
cortex
(mPFC)
regulation
anxiety.
Norepinephrine
(NE)
crucial
neuromodulator
arousal
vigilance
believed
be
responsible
for
many
anxiety
disorders.
NE
synthesized
locus
coeruleus
(LC),
which
sends
major
noradrenergic
inputs
mPFC.
Given
unique
properties
LC-mPFC
connections
heterogeneous
subpopulation
neurons
known
involved
regulating
anxiety-like
behaviors,
likely
modulates
PFC
function
cell-type
circuit-specific
manner.
In
working
memory
stress
response,
follows
inverted-U
model,
where
overly
high
low
release
associated
with
sub-optimal
neural
functioning.
contrast,
based
on
current
literature
review
individual
contributions
disorders,
we
propose
model
level-
adrenergic
receptor-dependent,
NE-PFC
modulation
Further,
advent
new
techniques
measure
unprecedented
spatial
temporal
resolution
will
significantly
help
us
understand
how
iScience,
Год журнала:
2025,
Номер
28(2), С. 111820 - 111820
Опубликована: Янв. 18, 2025
The
lateral
septum
(LS)
is
a
midline,
subcortical
structure
that
critical
regulator
of
social
behaviors.
Mouse
studies
have
identified
molecularly
distinct
neuronal
populations
within
the
LS,
which
control
specific
facets
behavior.
Despite
its
known
molecular
heterogeneity
in
mouse
and
role
regulating
behavior,
comprehensive
profiling
human
LS
has
not
been
performed.
Here,
we
conducted
single-nucleus
RNA
sequencing
(snRNA-seq)
to
generate
transcriptomic
profiles
compared
recently
collected
snRNA-seq
datasets.
Our
analyses
TRPC4
as
conserved
marker
while
FREM2
enriched
only
LS.
We
also
identify
cell
type
marked
by
OPRM1,
gene
encoding
μ-opioid
receptor.
Together,
these
results
highlight
transcriptional
robust
genes
for
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 16, 2024
Abstract
Because
opioid
withdrawal
is
an
intensely
aversive
experience,
persons
with
use
disorder
(OUD)
often
relapse
to
avoid
it.
The
lateral
septum
(LS)
a
forebrain
structure
that
important
in
aversion
processing,
and
previous
studies
have
linked
the
substance
disorders.
It
unclear,
however,
which
precise
LS
cell
types
might
contribute
maladaptive
state
of
withdrawal.
To
address
this,
we
used
single-nucleus
RNA-sequencing
interrogate
type
specific
gene
expression
changes
induced
by
chronic
morphine
We
discovered
globally
disrupted
transcriptional
profile
types,
but
Neurotensin-expressing
neurons
(
Nts
;
LS-
neurons)
were
selectively
activated
naloxone.
Using
two-photon
calcium
imaging
ex
vivo
electrophysiology,
next
demonstrate
receive
enhanced
glutamatergic
drive
morphine-dependent
mice
remain
hyperactivated
during
Finally,
showed
activating
silencing
regulates
pain
coping
behaviors
sociability.
Together,
these
results
suggest
are
key
neural
substrate
involved
establish
as
crucial
regulator
adaptive
behaviors,
specifically
pertaining
OUD.
