Frontiers in Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Июнь 8, 2023
Mathematical
modeling
has
played
a
significant
role
in
understanding
how
homeostatic
sleep
pressure
and
the
circadian
rhythm
interact
to
influence
sleep-wake
behavior.
Pain
sensitivity
is
also
affected
by
these
processes,
recent
experimental
results
have
measured
components
of
24
h
thermal
pain
humans.
To
analyze
rhythms
are
disruptions
behavior
shifts
rhythms,
we
introduce
dynamic
mathematical
model
for
regulation
states
intensity.The
consists
biophysically
based,
network
coupled
data-driven
functions
modulation
sensitivity.
This
sleep-wake-pain
validated
comparison
intensities
adult
humans
across
34
deprivation
protocol.We
use
predict
dysregulation
different
scenarios
shifts,
including
entrainment
new
environmental
light
activity
timing
as
occurs
with
jet
lag
chronic
restriction.
Model
show
that
increases
occur
under
conditions
increased
drive
nonlinear
rhythm,
leading
unexpected
decreased
some
scenarios.This
provides
useful
tool
management
predicting
alterations
due
varying
or
disrupted
schedules.
Frontiers in Neuroinformatics,
Год журнала:
2022,
Номер
16
Опубликована: Июнь 27, 2022
The
need
for
reproducible,
credible,
multiscale
biological
modeling
has
led
to
the
development
of
standardized
simulation
platforms,
such
as
widely-used
NEURON
environment
computational
neuroscience.
Developing
and
maintaining
over
several
decades
required
attention
competing
needs
backwards
compatibility,
evolving
computer
architectures,
addition
new
scales
physical
processes,
accessibility
users,
efficiency
flexibility
specialists.
In
order
meet
these
challenges,
we
have
now
substantially
modernized
NEURON,
providing
continuous
integration,
an
improved
build
system
release
workflow,
better
documentation.
With
help
a
source-to-source
compiler
NMODL
domain-specific
language
enhanced
NEURON's
ability
run
efficiently,
via
CoreNEURON
engine,
on
variety
hardware
including
GPUs.
Through
implementation
optimized
in-memory
transfer
mechanism
this
performance
backend
is
made
easily
accessible
training
model-development
paths
from
laptop
workstation
supercomputer
cloud
platform.
Similarly,
been
able
accelerate
reaction-diffusion
through
use
just-in-time
compilation.
We
show
that
efforts
growing
developer
base,
simpler
more
robust
software
distribution,
wider
range
supported
integration
with
other
scientific
workflows,
biophysical
biochemical
models.
Communications Biology,
Год журнала:
2023,
Номер
6(1)
Опубликована: Май 3, 2023
Abstract
Due
to
its
complex
and
multifaceted
nature,
developing
effective
treatments
for
epilepsy
is
still
a
major
challenge.
To
deal
with
this
complexity
we
introduce
the
concept
of
degeneracy
field
research:
ability
disparate
elements
cause
an
analogous
function
or
malfunction.
Here,
review
examples
epilepsy-related
at
multiple
levels
brain
organisation,
ranging
from
cellular
network
systems
level.
Based
on
these
insights,
outline
new
multiscale
population
modelling
approaches
disentangle
web
interactions
underlying
design
personalised
multitarget
therapies.
Crump
et
al.
have
provided
a
series
of
criteria
to
assess
animal
sentience
that
is
focused
on
the
perception
pain,
which
known
both
sensory
and
emotional
components.
They
also
provide
qualitative
scoring
system
data
address
eight
apply
this
paradigm
decapod
crustaceans.
The
laid
out
potential
be
applied
other
invertebrates
typically
thought
response
tissue
damage,
but
no
component
pain
perception.
Journal of Neuroscience,
Год журнала:
2023,
Номер
43(31), С. 5608 - 5622
Опубликована: Июль 14, 2023
Parvalbumin-expressing
interneurons
(PVINs)
play
a
crucial
role
within
the
dorsal
horn
of
spinal
cord
by
preventing
touch
inputs
from
activating
pain
circuits.
In
both
male
and
female
mice,
nerve
injury
decreases
PVINs'
output
via
mechanisms
that
are
not
fully
understood.
this
study,
we
show
PVINs
nerve-injured
mice
change
their
firing
pattern
tonic
to
adaptive.
To
examine
ionic
responsible
for
decreased
output,
used
reparametrized
Hodgkin-Huxley
type
model
PVINs,
which
predicted
(1)
transition
is
because
an
increased
contribution
small
conductance
calcium-activated
potassium
(SK)
channels,
enabled
(2)
impairment
in
intracellular
calcium
buffering
systems.
Analyzing
dynamics
further
demonstrated
generalized
Hopf
bifurcation
differentiates
two
types
state
transitions
observed
transient
PVINs.
Importantly,
mechanism
holds
true
when
embed
PVIN
neuronal
circuit
horn.
experimentally
validate
hypothesized
mechanism,
pharmacological
modulators
SK
channels
naive
become
adaptive
exposed
channel
activator,
adapting
return
on
blockade.
Our
work
provides
important
insights
into
cellular
underlying
after
highlights
potential
targets
new
effective
treatment
approaches
neuropathic
pain.
Nociceptive
sensory
neurons
convey
pain-related
signals
to
the
CNS
using
action
potentials.
Loss-of-function
mutations
in
voltage-gated
sodium
channel
Na
V
1.7
cause
insensitivity
pain
(presumably
by
reducing
nociceptor
excitability)
but
clinical
trials
seeking
treat
inhibiting
pharmacologically
have
struggled.
This
may
reflect
variable
contribution
of
excitability.
Contrary
claims
that
is
necessary
for
nociceptors
initiate
potentials,
we
show
can
achieve
similar
excitability
different
combinations
1.3,
1.7,
and
1.8.
Selectively
blocking
one
those
subtypes
reduces
only
if
other
are
weakly
expressed.
For
example,
relies
on
1.8
acutely
dissociated
responsibility
shifts
1.3
fourth
day
culture.
A
shift
dependence
occurs
vivo
after
inflammation,
impacting
ability
1.7-selective
inhibitor
PF-05089771
reduce
behavioral
tests.
Flexible
use
exemplifies
degeneracy
–
achieving
function
components
compromises
reliable
modulation
subtype-selective
inhibitors.
Identifying
dominant
subtype
predict
drug
efficacy
not
trivial.
Degeneracy
at
cellular
level
must
be
considered
when
choosing
targets
molecular
level.
Neurons
encounter
unavoidable
evolutionary
trade-offs
between
multiple
tasks.
They
must
consume
as
little
energy
possible
while
effectively
fulfilling
their
functions.
Cells
displaying
the
best
performance
for
such
multi-task
are
said
to
be
Pareto
optimal,
with
ion
channel
configurations
underpinning
functionality.
Ion
degeneracy,
however,
implies
that
can
lead
functionally
similar
behaviour.
Therefore,
instead
of
a
single
model,
neuroscientists
often
use
populations
models
distinct
combinations
ionic
conductances.
This
approach
is
called
population
(database
or
ensemble)
modelling.
It
remains
unclear,
which
parameters
in
vast
functional
more
likely
found
brain.
Here
we
argue
optimality
serve
guiding
principle
addressing
this
issue
by
helping
identify
subpopulations
conductance-based
perform
trade-off
economy
and
In
way,
high-dimensional
parameter
space
neuronal
might
reduced
geometrically
simple
low-dimensional
manifolds,
potentially
explaining
experimentally
observed
correlations.
Conversely,
inference
also
help
deduce
functions
from
Patch-seq
data.
summary,
promising
framework
improving
modelling
neurons
circuits.
Frontiers in Pain Research,
Год журнала:
2022,
Номер
3
Опубликована: Сен. 13, 2022
The
sensory
inflow
from
the
periphery
that
triggers
innocuous
and
painful
sensations
is
highly
complex,
capturing
key
elements
of
nature
any
stimulus,
its
location,
intensity,
duration,
converting
this
to
dynamic
action
potential
firing
across
a
wide
population
afferents.
While
afferents
are
specialized
detect
these
features,
their
input
spinal
cord
also
active
processing
modulation
there
which
determines
output,
drive
percept
experienced
behavioral
responses.
Focus
on
such
was
arguably
first
introduced
by
Melzack
Wall
in
Spinal
Cord
Gate
Control
theory.
This
theory
has
had
profound
influence
our
understanding
pain,
especially
processing,
as
well
leading
directly
development
clinical
interventions,
historical
importance
certainly
needs
be
fully
recognized.
However,
enormous
progress
we
making
function
somatosensory
system,
means
it
time
incorporate
newly
discovered
features
into
more
complex
accurate
model
modulation.
Frontiers in Neuroinformatics,
Год журнала:
2022,
Номер
16
Опубликована: Сен. 22, 2022
The
primary
somatosensory
cortex
(S1)
of
mammals
is
critically
important
in
the
perception
touch
and
related
sensorimotor
behaviors.
In
2015,
Blue
Brain
Project
(BBP)
developed
a
groundbreaking
rat
S1
microcircuit
simulation
with
over
31,000
neurons
207
morpho-electrical
neuron
types,
37
million
synapses,
incorporating
anatomical
physiological
information
from
wide
range
experimental
studies.
We
have
implemented
this
highly
detailed
complex
model
NetPyNE,
using
data
available
Neocortical
Microcircuit
Collaboration
Portal.
NetPyNE
provides
Python
high-level
interface
to
NEURON
allows
defining
complicated
multiscale
models
an
intuitive
declarative
standardized
language.
It
also
facilitates
running
parallel
simulations,
automates
optimization
exploration
parameters
supercomputers,
built-in
analysis
functions.
This
will
make
more
accessible
simpler
scale,
modify
extend
order
explore
research
questions
or
interconnect
other
existing
models.
Despite
some
implementation
differences,
preserved
original
cell
morphologies,
electrophysiological
responses
spatial
distribution
for
all
types;
connectivity
properties
1941
pathways,
including
synaptic
dynamics
short-term
plasticity
(STP).
simulations
produced
reasonable
firing
rates
activity
patterns
across
populations.
When
STP
was
included,
network
generated
1
Hz
oscillation
comparable
vitro
-like
state.
By
then
reducing
extracellular
calcium
concentration,
reproduced
vivo
states
asynchronous
activity.
These
results
validate
study
new
modeling
tool.
Simulated
local
field
potentials
(LFPs)
exhibited
realistic
oscillatory
features,
distance-
frequency-dependent
attenuation.
extended
by
adding
thalamic
circuits,
6
distinct
populations
intrathalamic,
thalamocortical
(TC)
corticothalamic
derived
data.
single
known
circuit-level
dynamics,
burst
tonic
modes
patterns,
providing
input
enabling
TC
interactions.
Overall,
our
work
widely
accessible,
data-driven
biophysically-detailed
circuits
that
can
be
employed
as
community
tool
researchers
neural
function
disease.
Frontiers in Network Physiology,
Год журнала:
2023,
Номер
3
Опубликована: Фев. 10, 2023
In
a
healthy
state,
pain
plays
an
important
role
in
natural
biofeedback
loops
and
helps
to
detect
prevent
potentially
harmful
stimuli
situations.
However,
can
become
chronic
as
such
pathological
condition,
losing
its
informative
adaptive
function.
Efficient
treatment
remains
largely
unmet
clinical
need.
One
promising
route
improve
the
characterization
of
pain,
with
that
potential
for
more
effective
therapies,
is
integration
different
data
modalities
through
cutting
edge
computational
methods.
Using
these
methods,
multiscale,
complex,
network
models
signaling
be
created
utilized
benefit
patients.
Such
require
collaborative
work
experts
from
research
domains
medicine,
biology,
physiology,
psychology
well
mathematics
science.
teams
requires
developing
common
language
level
understanding
prerequisite.
ways
meet
this
need
provide
easy
comprehend
overviews
certain
topics
within
domain.
Here,
we
propose
overview
on
topic
assessment
humans
researchers.
Quantifications
related
are
necessary
building
models.
defined
by
International
Association
Study
Pain
(IASP),
sensory
emotional
experience
thus,
it
cannot
measured
quantified
objectively.
This
results
clear
distinctions
between
nociception,
correlates
pain.
Therefore,
here
review
methods
assess
percept
nociception
biological
basis
humans,
goal
creating
roadmap
modelling
options.