bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Сен. 15, 2023
Abstract
The
cerebellar
cortex
contributes
to
diverse
behaviors
by
transforming
mossy
fiber
inputs
into
predictions
in
the
form
of
Purkinje
cell
(PC)
outputs,
and
then
refining
those
1
.
Molecular
layer
interneurons
(MLIs)
account
for
approximately
80%
inhibitory
2
,
are
vital
processing
1,3
MLIs
thought
primarily
inhibit
PCs
suppress
plasticity
excitatory
synapses
onto
PCs.
also
inhibit,
electrically
coupled
to,
other
4–7
but
functional
significance
these
connections
is
not
known
Behavioral
studies
suggest
that
cerebellar-dependent
learning
gated
disinhibition
PCs,
source
such
has
been
identified
8
Here
we
find
two
recently
recognized
MLI
subtypes
MLI1
MLI2,
have
highly
specialized
connectivity
allows
them
serve
very
different
roles.
MLI1s
each
other,
fire
synchronously
with
on
millisecond
time
scale
vivo
pause
PC
firing.
MLI2s
coupled,
they
disinhibit
well
suited
gating
These
findings
require
a
major
reevaluation
within
cerebellum
which
disinhibition,
powerful
circuit
motif
present
cerebral
elsewhere
9–17
greatly
increases
computational
power
flexibility
cerebellum.
They
synchronous
firing
electrically-coupled
helps
regulate
output
pausing
firing,
shown
evoke
precisely-timed
targets
18
Brain stimulation,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 1, 2025
Thalamocortical
sleep
spindles,
i.e.,
oscillatory
bursts
at
∼12-15
Hz
of
waxing
and
waning
amplitude,
are
a
hallmark
feature
non-rapid
eye
movement
(NREM)
believed
to
play
key
role
in
memory
reactivation
consolidation.
Generated
the
thalamus
projecting
neocortex
hippocampus,
they
phasically
modulated
by
neocortical
slow
oscillations
(<1
Hz)
turn
modulate
hippocampal
sharp-wave
ripples
(>80
Hz).
This
hierarchical
cross-frequency
nesting,
where
slower
group
faster
ones
into
certain
excitability
phases,
may
enable
phase-dependent
plasticity
neocortex,
spindles
have
thus
been
considered
windows
sleeping
brain.
However,
assumed
phasic
modulation
had
not
yet
demonstrated
for
spindles.
Utilizing
recently
developed
real-time
spindle
detection
algorithm,
we
applied
phase-triggered
transcranial
magnetic
stimulation
(TMS)
primary
motor
cortex
(M1)
hand
area
characterize
corticospinal
profile
via
evoked
potentials
(MEP).
MEPs
showed
net
suppression
during
driven
"pulse
inhibition"
its
falling
flank
with
no
inhibition
or
facilitation
peak,
rising
flank,
trough.
unidirectional
("asymmetric")
occurred
on
top
general
sleep-related
spindle-free
NREM
did
extend
refractory
post-spindle
periods.
We
conclude
that
exert
"asymmetric
pulsed
excitability.
These
findings
targeting
methods
future
studies
investigate
causal
synaptic
systems
consolidation
repetitively
relevant
phases.
Journal of Sleep Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 18, 2025
ABSTRACT
The
relationship
between
physical
activity
and
sleep
quality
is
a
critical
area
of
investigation,
given
the
importance
both
behaviours
for
health
disease.
Despite
common
use
running
wheels
to
assess
circadian
rhythms
exercise,
their
impact
on
has
not
been
thoroughly
explored.
Here,
we
present
detailed
analysis
how
voluntary
affected
sleep/wakefulness
duration,
architecture
electrophysiological
characteristics
in
mice.
Sequential
electroencephalogram
(EEG)
assessments
revealed
that
elicits
progressive
alteration
sleep/wake
configurations,
including
reduction
overall
daily
time
an
enhancement
consolidation.
These
modifications
exhibited
temporal
association
with
intensity
activities.
observed
changes
duration
partially
persist
even
after
discontinuation
running.
Spontaneous
also
gradually
changed
amplitude
and/or
frequency
EEG
theta
power
only
during
phase
but
rapid
eye
movement
(REMS).
In
vivo
endoscopic
calcium
imaging
freely
behaving
mice
REMS
were
accompanied
by
activation
largely
shared
yet
distinctive
neuronal
cohorts
within
hippocampal
CA1
region,
concomitant
oscillations
behaviours.
findings
highlight
dynamic
nature
regulation
response
exercise
suggest
played
pivotal
role
modulating
need
balance
wakefulness.
Synchronous
neuronal
ensembles
play
a
pivotal
role
in
the
consolidation
of
long-term
memory
hippocampus.
However,
their
organization
during
acquisition
spatial
remains
less
clear.
In
this
study,
we
used
population
voltage
imaging
to
investigate
synchronization
patterns
CA1
pyramidal
exploration
new
environment,
critical
phase
for
acquisition.
We
found
synchronous
comprising
approximately
40%
neurons,
firing
simultaneously
brief
windows
(∼25ms)
immobility
and
locomotion
novel
exploration.
Notably,
these
were
not
associated
with
contralateral
ripple
oscillations
but
instead
phase-locked
theta
waves
recorded
region.
Moreover,
subthreshold
membrane
potentials
neurons
exhibited
coherent
intracellular
depolarizing
peak
at
moment
synchrony.
Among
newly
formed
place
cells,
pairs
more
robust
displayed
distinct
place-specific
activities.
These
findings
underscore
coordinating
cells
different
fields.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 30, 2024
Individuals
with
the
22q11.2
deletion
syndrome,
one
of
strongest
genetic
risk
factors
for
schizophrenia,
demonstrate
cognitive
impairments
including
episodic
memory
dysfunction.
Place
cell
activity
excitatory
pyramidal
neurons
in
hippocampus
supporting
are
impaired
a
mouse
model
(
Df(16)A
+/-
).
While
dynamics
under
tight
inhibitory
control
by
multiple
subtypes
GABAergic
interneurons,
previous
studies
have
predominantly
focused
on
single
subtype
PV-expressing
interneurons;
there
not
yet
been
describing
functional
relationships
between
molecularly
identified
types
mice.
Here,
we
examined
interneuron
subtype-specific
dorsal
hippocampal
area
CA1
mice
during
random
foraging
and
spatial
reward
learning
tasks.
Capitalizing
3D
acousto-optical
deflector
two-photon
microscopy
post
hoc
immunohistochemical
identification,
found
that
exhibit
aberrant
responses
to
locations
delayed
enrichment
extinction.
interneurons
also
carry
markedly
reduced
information
subtype-dependent
manner.
We
observed
task-dependent
changes
correlation
structure
coactivity
among
subtypes,
suggesting
broadly
disorganized
microcircuit
functionality
mutant
Overall,
identify
widespread
heterogeneous
alterations
learning,
reflecting
flexibility
organization
microcircuits.
Our
study
provides
critical
insights
into
how
schizophrenia-risk
mutations
affect
local-circuit
interactions
diverse
navigation.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 11, 2023
Discrimination
and
generalization
are
crucial
brain-wide
functions
for
memory
object
recognition
that
utilize
pattern
separation
completion
computations.
Circuit
mechanisms
supporting
these
operations
remain
enigmatic.
We
show
lateral
entorhinal
cortex
glutamatergic
(LEC
GLU
)
GABAergic
GABA
projections
essential
memory.
Silencing
LEC
during
in
vivo
two-photon
imaging
increased
the
population
of
active
CA3
pyramidal
cells
but
decreased
activity
rates,
suggesting
a
sparse
coding
function
through
local
inhibition.
also
place
cell
remapping
between
different
environments
validating
this
circuit
drives
context
discrimination.
Optogenetic
mapping
confirmed
dominant
feedforward
inhibition
to
prevent
somatic
dendritic
spikes.
However,
conjunctively
suppresses
disinhibit
neuron
soma
selectively
boost
integrative
output
recurrent
network.
thus
promotes
generalization.
Indeed,
without
disinhibitory
input,
maps
similarity
contexts.
Our
findings
provide
whereby
long-range
cortico-hippocampal
inputs
bidirectionally
modulate
completion,
providing
neuronal
representations
with
dynamic
range
discrimination
Genetically
encoded
calcium
indicators
(GECIs)
such
as
GCaMP
are
invaluable
tools
in
neuroscience
to
monitor
neuronal
activity
using
optical
imaging.
The
viral
transduction
of
GECIs
is
commonly
used
target
expression
specific
brain
regions,
can
be
conveniently
with
any
mouse
strain
interest
without
the
need
for
prior
crossing
a
GECI
line
and
avoids
potential
hazards
due
chronic
during
development.
A
key
requirement
monitoring
an
indicator
that
itself
minimally
affects
activity.
Here,
common
adeno-associated
(AAV)
procedures,
we
describe
spatially
confined
aberrant
Ca
2+
micro-waves
slowly
travelling
through
hippocampus
following
GCaMP6,
GCaMP7
or
R-CaMP1.07
driven
by
synapsin
promoter
AAV-dependent
gene
transfer,
titre-dependent
fashion.
developed
hippocampal
CA1
CA3,
but
not
dentate
gyrus
(DG)
nor
neocortex,
were
typically
first
observed
at
4
weeks
after
transduction,
persisted
up
least
8
weeks.
phenomenon
was
robust,
across
laboratories
various
experimenters
setups.
Our
results
indicate
depend
on
titre
GECI,
density
well
targeted
region.
We
alternative
method
which
this
artifact.
show
-indicator
AAV
procedures
produce
artefactual
responses.
aim
raise
awareness
field
these
transduction-induced
provide
solution.Impact
statement:
Common
induce
waves
hippocampus.