bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 16, 2025
Compared
to
rodents,
inhibitory
interneurons
in
the
human
neocortex
exhibit
high
input
excitability
because
of
reduced
passive
ion
leakage
across
their
extracellular
membrane.
However,
regulation
intrinsic
by
voltage-gated
channels
activated
over
a
wide
range
membrane
potentials
remains
poorly
understood.
We
performed
whole-cell
patch-clamp
microelectrode
recordings
mouse
and
neocortical
slices
obtained
from
surgically
resected
non-pathological
brain
tissue
finding
that
Kir
control
electrical
resistance
parvalbumin
(Pvalb)
neurons
an
identical
manner
mouse.
Molecular
analyses
revealed
predominantly
Kir3.1
Kir3.2
Pvalb
both
species.
Using
synaptically
connected
neuron
pairs
computational
model,
we
demonstrated
physiological
activation
inhibits
during
postsynaptic
evoked
presynaptic
neurogliaform
cells.
The
similarity
Kir-mediated
inhibition
species
suggests
it
is
archetypal
property
neurons.
Science,
Journal Year:
2023,
Volume and Issue:
382(6667)
Published: Oct. 12, 2023
Human
cortex
transcriptomic
studies
have
revealed
a
hierarchical
organization
of
γ-aminobutyric
acid-producing
(GABAergic)
neurons
from
subclasses
to
high
diversity
more
granular
types.
Rapid
GABAergic
neuron
viral
genetic
labeling
plus
Patch-seq
(patch-clamp
electrophysiology
single-cell
RNA
sequencing)
sampling
in
human
brain
slices
was
used
reliably
target
and
analyze
individual
This
characterization
elucidated
transitions
between
PVALB
SST
subclasses,
morphological
heterogeneity
within
an
abundant
type,
identified
multiple
spatially
distinct
types
the
primate-specialized
double
bouquet
cells
(DBCs),
shed
light
on
cellular
differences
homologous
mouse
neocortical
These
results
highlight
importance
multimodal
phenotypic
for
refinement
emerging
cell
type
taxonomies
understanding
conserved
specialized
properties
Nature Neuroscience,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 14, 2024
Alzheimer's
disease
(AD)
is
the
leading
cause
of
dementia
in
older
adults.
Although
AD
progression
characterized
by
stereotyped
accumulation
proteinopathies,
affected
cellular
populations
remain
understudied.
Here
we
use
multiomics,
spatial
genomics
and
reference
atlases
from
BRAIN
Initiative
to
study
middle
temporal
gyrus
cell
types
84
donors
with
varying
pathologies.
This
cohort
includes
33
male
51
female
donors,
an
average
age
at
time
death
88
years.
We
used
quantitative
neuropathology
place
along
a
pseudoprogression
score.
Pseudoprogression
analysis
revealed
two
phases:
early
phase
slow
increase
pathology,
presence
inflammatory
microglia,
reactive
astrocytes,
loss
somatostatin
Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: May 23, 2023
Alzheimer's
disease
(AD)
is
the
most
common
cause
of
dementia
in
older
adults.
Neuropathological
and
imaging
studies
have
demonstrated
a
progressive
stereotyped
accumulation
protein
aggregates,
but
underlying
molecular
cellular
mechanisms
driving
AD
progression
vulnerable
cell
populations
affected
by
remain
coarsely
understood.
The
current
study
harnesses
single
spatial
genomics
tools
knowledge
from
BRAIN
Initiative
Cell
Census
Network
to
understand
impact
on
middle
temporal
gyrus
types.
We
used
image-based
quantitative
neuropathology
place
84
donors
spanning
spectrum
pathology
along
continuous
pseudoprogression
score
multiomic
technologies
profile
nuclei
each
donor,
mapping
their
transcriptomes,
epigenomes,
coordinates
type
reference
with
unprecedented
resolution.
Temporal
analysis
cell-type
proportions
indicated
an
early
reduction
Somatostatin-expressing
neuronal
subtypes
late
decrease
supragranular
intratelencephalic-projecting
excitatory
Parvalbumin-expressing
neurons,
increases
disease-associated
microglial
astrocytic
states.
found
complex
gene
expression
differences,
ranging
global
type-specific
effects.
These
effects
showed
different
patterns
indicating
diverse
perturbations
as
function
progression.
A
subset
particularly
severe
phenotype,
which
correlated
steeper
cognitive
decline.
created
freely
available
public
resource
explore
these
data
accelerate
progress
research
at
SEA-AD.org.
Imaging Neuroscience,
Journal Year:
2024,
Volume and Issue:
2, P. 1 - 35
Published: April 1, 2024
Abstract
In
recent
years,
brain
research
has
indisputably
entered
a
new
epoch,
driven
by
substantial
methodological
advances
and
digitally
enabled
data
integration
modelling
at
multiple
scales—from
molecules
to
the
whole
brain.
Major
are
emerging
intersection
of
neuroscience
with
technology
computing.
This
science
combines
high-quality
research,
across
scales,
culture
multidisciplinary
large-scale
collaboration,
translation
into
applications.
As
pioneered
in
Europe’s
Human
Brain
Project
(HBP),
systematic
approach
will
be
essential
for
meeting
coming
decade’s
pressing
medical
technological
challenges.
The
aims
this
paper
to:
develop
concept
decade
digital
discuss
community
large,
identify
points
convergence,
derive
therefrom
scientific
common
goals;
provide
framework
current
future
development
EBRAINS,
infrastructure
resulting
from
HBP’s
work;
inform
engage
stakeholders,
funding
organisations
institutions
regarding
research;
address
transformational
potential
comprehensive
models
artificial
intelligence,
including
machine
learning
deep
learning;
outline
collaborative
that
integrates
reflection,
dialogues,
societal
engagement
on
ethical
opportunities
challenges
as
part
research.
Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(5), P. 114212 - 114212
Published: May 1, 2024
Diverse
types
of
inhibitory
interneurons
(INs)
impart
computational
power
and
flexibility
to
neocortical
circuits.
Whereas
markers
for
different
IN
in
cortical
layers
2-6
(L2-L6)
have
been
instrumental
generating
a
wealth
functional
insights,
only
the
recent
identification
selective
marker
(neuron-derived
neurotrophic
factor
[NDNF])
has
opened
comparable
opportunities
INs
L1
(L1INs).
However,
at
present
we
know
very
little
about
connectivity
NDNF
L1INs
with
other
types,
their
input-output
conversion,
existence
potential
L1IN
subtypes.
Here,
report
pervasive
inhibition
L2/3
(including
parvalbumin
vasoactive
intestinal
peptide
INs)
by
L1INs.
Intersectional
genetics
revealed
similar
physiology
subpopulation
co-expressing
neuropeptide
Y.
Finally,
prominently
selectively
engage
persistent
firing,
physiological
hallmark
disconnecting
output
from
current
input.
Collectively,
our
work
therefore
identifies
as
specialized
master
regulators
superficial
neocortex
according
top-down
afferents.
