Proceedings of the National Academy of Sciences,
Год журнала:
2019,
Номер
116(52), С. 27063 - 27073
Опубликована: Дек. 16, 2019
Perineuronal
nets
(PNNs),
a
complex
of
extracellular
matrix
molecules
that
mostly
surround
GABAergic
neurons
in
various
brain
regions,
play
critical
role
synaptic
plasticity.
The
function
and
cellular
mechanisms
PNNs
memory
consolidation
reconsolidation
processes
are
still
not
well
understood.
We
hypothesized
protect
long-term
by
limiting
feedback
inhibition
from
parvalbumin
(PV)
interneurons
to
projection
neurons.
Using
behavioral,
electrophysiological,
optogenetic
approaches,
we
investigated
the
fear
potentiation
(LTP).
made
discovery
formation
was
promoted
events
hippocampus
(HP),
also
demonstrated
PNN
both
HP
anterior
cingulate
cortex
(ACC)
is
essential
for
recent
remote
memories.
Removal
resulted
evident
LTP
impairments,
which
were
rescued
acute
application
picrotoxin,
GABAA
receptor
blocker,
indicating
enhanced
cause
impairments
induced
removal.
Moreover,
removal
switched
receptor-mediated
depression
through
presynaptic
mechanism.
Furthermore,
reduced
activity
PV
surrounded
regulated
theta
oscillations
during
consolidation.
Finally,
optogenetically
suppressing
impairment
caused
PNNs.
Altogether,
these
results
unveil
surrounding
protecting
contextual
regulation
neuron
GABA
release.
Science,
Год журнала:
2022,
Номер
377(6601), С. 80 - 86
Опубликована: Май 26, 2022
Activation
of
microglia
in
the
spinal
cord
dorsal
horn
after
peripheral
nerve
injury
contributes
to
development
pain
hypersensitivity.
How
activated
selectively
enhance
activity
nociceptive
circuits
is
not
well
understood.
We
discovered
that
injury,
degrade
extracellular
matrix
structures,
perineuronal
nets
(PNNs),
lamina
I
horn.
Lamina
PNNs
enwrap
spinoparabrachial
projection
neurons,
which
integrate
information
and
convey
it
supraspinal
brain
regions
induce
sensation.
Degradation
by
enhances
neurons
induces
pain-related
behaviors.
Thus,
injury-induced
degradation
a
mechanism
augment
output
cause
Cellular and Molecular Immunology,
Год журнала:
2021,
Номер
18(11), С. 2472 - 2488
Опубликована: Авг. 19, 2021
Abstract
Microglia
shape
the
synaptic
environment
in
health
and
disease,
but
synapses
do
not
exist
a
vacuum.
Instead,
pre-
postsynaptic
terminals
are
surrounded
by
extracellular
matrix
(ECM),
which
together
with
glia
comprise
four
elements
of
contemporary
tetrapartite
synapse
model.
While
research
this
area
is
still
just
beginning,
accumulating
evidence
points
toward
novel
role
for
microglia
regulating
ECM
during
normal
brain
homeostasis,
such
processes
may,
turn,
become
dysfunctional
disease.
As
it
relates
to
synapses,
reported
modify
perisynaptic
matrix,
diffuse
that
surrounds
dendritic
axonal
terminals,
as
well
perineuronal
nets
(PNNs),
specialized
reticular
formations
compact
enwrap
neuronal
subsets
stabilize
proximal
synapses.
The
interconnected
relationship
between
they
embedded
suggests
alterations
one
structure
necessarily
affect
dynamics
other,
may
need
sculpt
within.
Here,
we
provide
an
overview
microglial
regulation
PNNs,
propose
candidate
mechanisms
these
structures
be
modified,
present
implications
modifications
homeostasis
Molecular Psychiatry,
Год журнала:
2022,
Номер
27(8), С. 3192 - 3203
Опубликована: Июнь 27, 2022
Abstract
All
components
of
the
CNS
are
surrounded
by
a
diffuse
extracellular
matrix
(ECM)
containing
chondroitin
sulphate
proteoglycans
(CSPGs),
heparan
(HSPGs),
hyaluronan,
various
glycoproteins
including
tenascins
and
thrombospondin,
many
other
molecules
that
secreted
into
ECM
bind
to
components.
In
addition,
some
neurons,
particularly
inhibitory
GABAergic
parvalbumin-positive
(PV)
interneurons,
more
condensed
cartilage-like
called
perineuronal
nets
(PNNs).
PNNs
surround
soma
proximal
dendrites
as
net-like
structures
synapses.
Attention
has
focused
on
role
in
control
plasticity,
but
it
is
now
clear
also
play
an
important
part
modulation
memory.
this
review
we
summarize
ECM,
PNNs,
types
memory
their
participation
pathology.
being
considered
target
for
treatment
impaired
There
potential
targets
mainly
through
sulphation,
binding,
production
CSPGs
they
contain
or
digestion
sulphated
glycosaminoglycans.
Science,
Год журнала:
2023,
Номер
380(6644), С. 543 - 551
Опубликована: Май 4, 2023
The
ability
to
form
precise,
episodic
memories
develops
with
age,
young
children
only
able
gist-like
that
lack
precision.
cellular
and
molecular
events
in
the
developing
hippocampus
underlie
emergence
of
episodic-like
memory
are
unclear.
In
mice,
absence
a
competitive
neuronal
engram
allocation
process
immature
precluded
formation
sparse
engrams
precise
until
fourth
postnatal
week,
when
inhibitory
circuits
mature.
This
age-dependent
shift
precision
involved
functional
maturation
parvalbumin-expressing
interneurons
subfield
CA1
through
assembly
extracellular
perineuronal
nets,
which
is
necessary
sufficient
for
onset
allocation,
formation,
Nature,
Год журнала:
2024,
Номер
629(8011), С. 402 - 409
Опубликована: Апрель 17, 2024
Abstract
Throughout
life,
neuronal
networks
in
the
mammalian
neocortex
maintain
a
balance
of
excitation
and
inhibition,
which
is
essential
for
computation
1,2
.
Deviations
from
balanced
state
have
been
linked
to
neurodevelopmental
disorders,
severe
disruptions
result
epilepsy
3–5
To
balance,
microcircuits
composed
excitatory
inhibitory
neurons
sense
alterations
neural
activity
adjust
connectivity
function.
Here
we
identify
signalling
pathway
adult
mouse
that
activated
response
increased
network
activity.
Overactivation
signalled
through
an
increase
levels
BMP2,
growth
factor
well
known
its
role
as
morphogen
embryonic
development.
BMP2
acts
on
parvalbumin-expressing
(PV)
interneurons
transcription
SMAD1,
controls
array
glutamatergic
synapse
proteins
components
perineuronal
nets.
PV-interneuron-specific
disruption
BMP2–SMAD1
accompanied
by
loss
innervation
PV
cells,
underdeveloped
nets
decreased
excitability.
Ultimately,
this
impairment
functional
recruitment
disrupts
cortical
excitation–inhibition
with
mice
exhibiting
spontaneous
epileptic
seizures.
Our
findings
suggest
developmental
repurposed
stabilize
brain.
Frontiers in Molecular Neuroscience,
Год журнала:
2018,
Номер
11
Опубликована: Авг. 3, 2018
Perineuronal
nets
(PNN)
are
extracellular
matrix
(ECM)
assemblies
that
preferentially
ensheath
parvalbumin
(PV)
expressing
interneurons.
Converging
evidence
indicates
PV
cells
and
PNN
impaired
in
a
variety
of
neurological
disorders.
development
maintenance
is
necessary
for
number
processes
within
the
CNS,
including
regulation
GABAergic
cell
function,
protection
neurons
from
oxidative
stress,
closure
developmental
critical
period
plasticity
windows.
Understanding
functions
may
be
essential
characterizing
mechanisms
altered
cortical
excitability
observed
neurodegenerative
neurodevelopmental
Indeed,
abnormalities
have
been
post-mortem
brain
tissues
patients
with
schizophrenia
Alzheimer's
disease.
There
PNNs
enhanced
activity
its
key
regulator
metalloproteinase-9
(MMP-9)
Fragile
X
Syndrome,
common
genetic
cause
autism.
MMP-9,
protease
cleaves
ECM,
differentially
regulated
these
Despite
this,
few
studies
addressed
interactions
between
expression,
MMP-9
neuronal
excitability.
In
this
review,
we
highlight
current
CNS
disorders
associated
network
function
levels,
emphasizing
need
future
work
targeting
pathophysiology
therapeutic
treatment
