bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 5, 2024
Abstract
To
model
the
dynamics
of
neuron
membrane
excitability
many
models
can
be
considered,
from
most
biophysically
detailed
to
highest
level
phenomenological
description.
Recent
works
at
single
have
shown
importance
taking
into
account
evolution
slow
variables
such
as
ionic
concentration.
A
reduction
a
integrate-and-fire
family
is
interesting
then
go
large
network
models.
In
this
paper,
we
introduce
way
consider
impairment
regulation
by
adding
third,
slow,
variable
adaptive
Exponential
(AdEx).
We
implement
and
simulate
including
model.
find
that
was
able
generate
normal
epileptic
discharges.
This
should
useful
for
design
simulations
pathological
states.
Abstract
The
composition
of
the
extracellular
milieu
can
vary
significantly
under
physiological
and
pathological
conditions,
thereby
altering
functional
set
point
brain
cells.
While
global
changes
in
are
known
to
affect
network
activity,
a
detailed
understanding
how
specific
ion
species
impact
individual
cells
remains
elusive.
Current
modulation
methods
involve
use
diluted
salts,
such
as
KCl,
where
lack
precise
control
complicates
data
interpretation.
This
study
achieves
enhanced
resolution
by
using
miniaturized
iontronic
micropipette.
micropipette,
with
tip
filled
polyelectrolyte
an
outlet
size
below
2
µm,
allows
for
on‐demand
ionic
manipulation
single
cells,
without
simultaneous
co‐delivery
solvents
or
other
solutes.
Electrical,
chemical,
optical
characterizations,
supported
computational
modeling,
confirm
device's
high
spatial
temporal
precision.
Validated
hippocampal
slices,
device
demonstrates
release
potassium
ions
(K⁺),
low
current
(<200
nA),
that
effectively,
rapidly,
reversibly
modulates
individually
targeted
neurons
astrocytes.
These
findings
underscore
potential
micropipettes
elucidate
distinct
responses
neuronal
glial
local
milieu,
offering
insights
neuroscience
research
therapeutic
innovation.
PLoS Computational Biology,
Год журнала:
2024,
Номер
20(3), С. e1011874 - e1011874
Опубликована: Март 4, 2024
The
biophysical
properties
of
neurons
not
only
affect
how
information
is
processed
within
cells,
they
can
also
impact
the
dynamical
states
network.
Specifically,
cellular
dynamics
action-potential
generation
have
shown
relevance
for
setting
(de)synchronisation
state
tonically
spiking
typically
fall
into
one
three
qualitatively
distinct
types
that
arise
from
mathematical
bifurcations
voltage
at
onset
spiking.
Accordingly,
changes
in
ion
channel
composition
or
even
external
factors,
like
temperature,
been
demonstrated
to
switch
network
behaviour
via
spike
bifurcation
and
hence
its
associated
type.
A
thus
far
less
addressed
modulator
neuronal
morphology.
Based
on
simplified
anatomically
realistic
neuron
models,
we
show
here
extent
dendritic
arborisation
has
an
influence
type
therefore
larger
trees
prime
in-phase-synchronised
splayed-out
activity
weakly
coupled
networks,
contrast
cells
with
otherwise
identical
yet
smaller
dendrites.
Our
insights
hold
generic
multicompartmental
classes
models
(from
ball-and-stick-type
reconstructed
models)
establish
a
connection
between
morphology
susceptibility
neural
tissue
synchronisation
health
disease.
Journal of Neural Engineering,
Год журнала:
2024,
Номер
21(2), С. 021002 - 021002
Опубликована: Апрель 1, 2024
Abstract
Objective
:
Epilepsy
is
a
complex
disease
spanning
across
multiple
scales,
from
ion
channels
in
neurons
to
neuronal
circuits
the
entire
brain.
Over
past
decades,
computational
models
have
been
used
describe
pathophysiological
activity
of
epileptic
brain
different
aspects.
Traditionally,
each
model
can
aid
optimizing
therapeutic
interventions,
therefore,
providing
particular
view
design
strategies
for
treating
epilepsy.
As
result,
most
studies
are
concerned
with
generating
specific
that
help
us
understand
certain
machinery
pathological
state.
Those
vary
complexity
and
biological
accuracy,
system-level
often
lacking
details.
Approach
Here,
we
review
various
types
epilepsy
discuss
their
potential
approaches
scenarios,
including
drug
discovery,
surgical
strategies,
stimulation,
seizure
prediction.
We
propose
need
consider
an
integrated
approach
unified
modelling
framework
scales
Our
proposal
based
on
recent
increase
power,
which
has
opened
up
possibility
unifying
those
into
simulations
unprecedented
level
detail.
Main
results
A
multi-scale
bridge
gap
between
biologically
detailed
models,
address
molecular
cellular
questions,
brain-wide
abstract
account
neurological
behavioural
observations.
Significance
With
these
efforts,
move
toward
next
generation
capable
connecting
features,
such
as
channel
properties,
standard
clinical
measures
severity.
PLoS Computational Biology,
Год журнала:
2024,
Номер
20(8), С. e1011751 - e1011751
Опубликована: Авг. 12, 2024
Slow
brain
rhythms,
for
example
during
slow-wave
sleep
or
pathological
conditions
like
seizures
and
spreading
depolarization,
can
be
accompanied
by
oscillations
in
extracellular
potassium
concentration.
Such
slow
rhythms
typically
have
a
lower
frequency
than
tonic
action-potential
firing.
They
are
assumed
to
arise
from
network-level
mechanisms,
involving
synaptic
interactions
delays,
intrinsically
bursting
neurons.
Neuronal
burst
generation
is
commonly
attributed
ion
channels
with
kinetics.
Here,
we
explore
an
alternative
mechanism
generically
available
all
neurons
class
I
excitability.
It
based
on
the
interplay
of
fast-spiking
voltage
dynamics
one-dimensional
concentration,
mediated
activity
Na
+
/K
-ATPase.
We
use
bifurcation
analysis
complete
system
as
well
slow-fast
method
reveal
that
this
coupling
suffices
generate
hysteresis
loop
organized
around
bistable
region
emerges
saddle-node
bifurcation–a
common
feature
excitable
Depending
strength
-ATPase,
bursts
generated
pump-induced
shearing
structure,
spiking
tonic,
cells
silenced
via
depolarization
block.
suggest
transitions
between
these
result
disturbances
regulation,
such
glial
malfunction
hypoxia
affecting
-ATPase
activity.
The
identified
minimal
mechanistic
model
outlining
sodium-potassium
pump’s
generic
contribution
can,
therefore,
contribute
better
understanding
pathologies
epilepsy
syndromes
and,
potentially,
inform
therapeutic
strategies.
International Journal of Bifurcation and Chaos,
Год журнала:
2024,
Номер
34(03)
Опубликована: Март 11, 2024
In
this
paper,
a
tripartite
synapse
network
is
constructed
to
examine
external
and
internal
triggering
factors
of
epilepsy
transition
propagation
in
neurons
with
the
Epileptor-2
model.
We
first
explore
stimuli
environment
that
induce
epileptic
activities
behaviors
among
Ictal
Discharges
(IDs)
Interictal
(IIDs)
states.
The
higher
strength
abruptness
stimuli,
more
severe
occurrence
within
reasonable
range
parameters.
Then
for
factors,
results
network,
which
improved
by
combining
model
astrocyte
means
ion
exchange
new
connections,
show
astrocytes
can
transmit
normal
physiological
activity
information
filter
out
abnormal
discharge
neurons.
One
causes
seizures
release
glial
neurotransmitters
astrocytes.
excessive
glutamate
state
transit
from
nonepileptic
IIDs,
IDs
tonic,
while
adenosine
triphosphate
alleviate
epilepsy.
Meanwhile,
dysfunction
an
astrocyte-free
also
lead
seizures,
ability
becomes
weaker
than
network.
Our
research
expected
provide
some
theoretical
basis
therapeutic
approach
curing
intracellular
extracellular
contexts.
eNeuro,
Год журнала:
2024,
Номер
11(10), С. ENEURO.0308 - 24.2024
Опубликована: Окт. 1, 2024
Experimental
evidence
showed
that
an
increase
in
intracellular
chloride
concentration
([Cl−]i)
caused
by
gamma-aminobutyric
acid
(GABA)
input
can
promote
epileptic
firing
activity,
but
the
actual
mechanisms
remain
elusive.
Here
this
theoretical
work,
we
show
influx
of
and
concomitant
bicarbonate
ion
stretchy="false">(HCO3−l−]i
.
found
increases,
system
exhibits
saddle–node
bifurcation,
above
which
spectrum
intensive
firing,
periodic
bursting
interrupted
depolarization
block
(DB)
state,
eventually
stable
DB
through
Hopf
bifurcation.
demonstrate
only
stimuli
together
with
overflow="scroll">HCO3−
switch
GABA's
effect
excitation
leads
series
seizure-like
events
(SLEs).
Exposure
low
stretchy="false">[K+]bath
drive
neurons
high
concentrations
downward
lower
levels
,
during
it
could
also
trigger
SLEs
depending
on
exchange
rate
bath.
Our
analysis
simulation
results
how
competition
between
stimuli-induced
accumulation
mathvariant="normal">bath
application-induced
decrease
regulates
helps
understand
fundamental
ionic
dynamics
SLE.
