Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(17)
Опубликована: Апрель 19, 2024
Hippocampal
somatostatin-expressing
(
Sst
)
GABAergic
interneurons
(INs)
exhibit
considerable
anatomical
and
functional
heterogeneity.
Recent
single-cell
transcriptome
analyses
have
provided
a
comprehensive
-IN
subpopulations
census,
plausible
molecular
ground
truth
of
neuronal
identity
whose
links
to
specific
functionality
remain
incomplete.
Here,
we
designed
an
approach
identify
access
-INs
based
on
transcriptomic
features.
Four
mouse
models
single
or
combinatorial
Cre-
Flp-
expression
differentiated
functionally
distinct
CA1
hippocampal
Sst-
INs
that
largely
tiled
the
morpho-functional
parameter
space
superfamily.
Notably,
Sst;;Tac1
intersection
revealed
population
bistratified
preferentially
synapsed
onto
fast-spiking
(FS-INs)
were
sufficient
interrupt
their
firing.
In
contrast,
Ndnf;;Nkx2-1
identified
oriens
lacunosum-moleculare
predominantly
targeted
pyramidal
neurons,
avoiding
FS-INs.
Overall,
our
results
provide
framework
translate
into
discrete
subtypes
capture
diverse
specializations
-INs.
The
medial
prefrontal
cortex
(mPFC)
and
its
abundant
connections
with
other
brain
regions
play
key
roles
in
memory,
cognition,
decision
making,
social
behaviors,
mood.
Dysfunction
mPFC
is
implicated
psychiatric
disorders
which
these
behaviors
go
awry.
prolonged
maturation
of
likely
enables
complex
to
emerge,
but
also
increases
their
vulnerability
disruption.
Many
foundational
studies
have
characterized
either
synaptic
or
behavioral
development
without
establishing
between
them.
Here,
we
review
this
rich
body
literature,
aligning
major
events
the
behaviors.
We
focus
on
emotional
memory
cognitive
flexibility,
highlight
new
work
linking
circuit
disruption
alterations
disease
models.
advance
hypotheses
about
causal
propose
research
strategies
establish
an
integrated
understanding
neural
architecture
repertoires.
Cell,
Год журнала:
2022,
Номер
185(4), С. 672 - 689.e23
Опубликована: Фев. 1, 2022
ChRmine,
a
recently
discovered
pump-like
cation-conducting
channelrhodopsin,
exhibits
puzzling
properties
(large
photocurrents,
red-shifted
spectrum,
and
extreme
light
sensitivity)
that
have
created
new
opportunities
in
optogenetics.
ChRmine
its
homologs
function
as
ion
channels
but,
by
primary
sequence,
more
closely
resemble
pump
rhodopsins;
mechanisms
for
passive
channel
conduction
this
family
remained
mysterious.
Here,
we
present
the
2.0
Å
resolution
cryo-EM
structure
of
revealing
architectural
features
atypical
channelrhodopsins:
trimeric
assembly,
short
transmembrane-helix
3,
twisting
extracellular-loop
1,
large
vestibules
within
monomer,
an
opening
at
trimer
interface.
We
applied
to
design
three
proteins
(rsChRmine
hsChRmine,
conferring
further
high-speed
properties,
respectively,
frChRmine,
combining
faster
performance)
suitable
fundamental
neuroscience
opportunities.
These
results
illuminate
gating
channelrhodopsins
point
way
toward
structure-guided
creation
applications
across
biology.
Neuron,
Год журнала:
2022,
Номер
110(5), С. 841 - 856.e6
Опубликована: Янв. 3, 2022
Female
mice
exhibit
opposing
social
behaviors
toward
males
depending
on
their
reproductive
state:
virgins
display
sexual
receptivity
(lordosis
behavior),
while
lactating
mothers
attack.
How
a
change
in
state
produces
qualitative
switch
behavioral
response
to
the
same
conspecific
stimulus
is
unknown.
Using
single-cell
RNA-seq,
we
identify
two
distinct
subtypes
of
estrogen
receptor-1-positive
neurons
ventrolateral
subdivision
female
ventromedial
hypothalamus
(VMHvl)
and
demonstrate
that
they
causally
control
aggressiveness
mothers,
respectively.
Between-
within-subject
bulk-calcium
recordings
from
each
subtype
reveal
aggression-specific
cells
acquire
an
increased
responsiveness
cues
during
transition
virginity
maternity,
mating-specific
population
appears
unchanged.
These
results
reproductive-state-dependent
changes
relative
activity
transcriptomically
neural
can
underlie
categorical
switches
behavior
associated
with
physiological
changes.
Systemic
metabolism
has
to
be
constantly
adjusted
the
variance
of
food
intake
and
even
prepared
for
anticipated
changes
in
nutrient
availability.
Therefore,
brain
integrates
multiple
homeostatic
signals
with
numerous
cues
that
predict
future
deviations
energy
supply.
Recently,
our
understanding
neural
pathways
underlying
these
regulatory
principles-as
well
as
their
convergence
hypothalamus
key
coordinator
intake,
expenditure,
glucose
metabolism-have
been
revealed.
These
advances
have
changed
view
brain-dependent
control
metabolic
physiology.
In
this
Review,
we
discuss
new
concepts
about
how
alterations
contribute
development
prevalent
diseases
such
obesity
type
2
diabetes
mellitus
emerging
knowledge
may
provide
targets
treatment.
Neuron,
Год журнала:
2023,
Номер
111(24), С. 4006 - 4023.e10
Опубликована: Дек. 1, 2023
Phosphorylation
of
α-synuclein
at
the
serine-129
site
(α-syn
Ser129P)
is
an
established
pathologic
hallmark
synucleinopathies
and
a
therapeutic
target.
In
physiologic
states,
only
fraction
α-syn
phosphorylated
this
site,
most
studies
have
focused
on
roles
post-translational
modification.
We
found
that
unlike
wild-type
(WT)
α-syn,
which
widely
expressed
throughout
brain,
overall
pattern
Ser129P
restricted,
suggesting
intrinsic
regulation.
Surprisingly,
preventing
blocked
activity-dependent
synaptic
attenuation
by
α-syn—thought
to
reflect
its
normal
function.
Exploring
mechanisms,
we
neuronal
activity
augments
Ser129P,
trigger
for
protein-protein
interactions
are
necessary
mediating
function
synapse.
AlphaFold2-driven
modeling
membrane-binding
simulations
suggest
scenario
where
induces
conformational
changes
facilitate
with
binding
partners.
Our
experiments
offer
new
conceptual
platform
investigating
role
Ser129
in
synucleinopathies,
implications
drug
development.
