Molecular and Cellular Neuroscience,
Год журнала:
2023,
Номер
125, С. 103858 - 103858
Опубликована: Май 10, 2023
High
turnover
rates
of
synaptic
proteins
imply
that
synapses
constantly
need
to
replace
their
constituent
building
blocks.
This
requires
sophisticated
supply
chains
and
potentially
exposes
shortages
as
they
compete
for
limited
resources.
Interestingly,
competition
in
neurons
has
been
observed
at
different
scales.
Whether
it
is
receptors
binding
sites
inside
a
single
synapse
or
fighting
resources
grow.
Here
we
review
the
implications
such
function
plasticity.
We
identify
multiple
mechanisms
use
safeguard
themselves
against
fundamental
neurologistic
trade-off
governing
sizes
reserve
pools
essential
At
presynaptic
active
zones
(AZs),
conserved
scaffold
protein
architectures
control
synaptic
vesicle
(SV)
release
by
defining
the
nanoscale
distribution
and
density
of
voltage-gated
Ca
2+
channels
(VGCCs).
While
AZs
can
potentiate
SV
in
minutes
range,
we
lack
an
understanding
how
AZ
components
VGCCs
engage
into
potentiation.
We
here
establish
dynamic,
intravital
single-molecule
imaging
endogenously
tagged
proteins
at
Drosophila
undergoing
homeostatic
During
potentiation,
numbers
α1
VGCC
subunit
Cacophony
(Cac)
increased
per
AZ,
while
their
mobility
decreased
compacted.
These
dynamic
Cac
changes
depended
on
interaction
between
channel’s
intracellular
carboxyl
terminus
membrane-close
amino-terminal
region
ELKS-family
Bruchpilot,
whose
compacted
drastically.
The
Cac-ELKS/Bruchpilot
was
also
needed
for
sustained
Our
analysis
illustrates
couples
to
dynamics
a
state
Synapses
are
endowed
with
the
flexibility
to
change
through
experience,
but
must
be
sufficiently
stable
last
a
lifetime.
This
tension
is
illustrated
at
Drosophila
neuromuscular
junction
(NMJ),
where
two
motor
inputs
that
differ
in
structural
and
functional
properties
coinnervate
most
muscles
coordinate
locomotion.
To
stabilize
NMJ
activity,
neurons
augment
neurotransmitter
release
following
diminished
postsynaptic
glutamate
receptor
functionality,
termed
presynaptic
homeostatic
potentiation
(PHP).
How
these
distinct
contribute
PHP
plasticity
remains
enigmatic.
We
have
used
botulinum
neurotoxin
selectively
silence
each
input
resolve
their
roles
PHP,
demonstrating
specific:
Chronic
(genetic)
targets
tonic
MN-Ib,
active
zone
remodeling
enhances
Ca
2+
influx
promote
increased
release.
In
contrast,
acute
(pharmacological)
increases
vesicle
pools
potentiate
phasic
MN-Is.
Thus,
modulations
nanoarchitecture,
pools,
collaborate
enable
input-specific
expression.
Frontiers in Cellular Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Июль 13, 2023
Presynaptic
plasticity
is
an
activity-dependent
change
in
the
neurotransmitter
release
and
plays
a
key
role
dynamic
modulation
of
synaptic
strength.
Particularly,
presynaptic
potentiation
mediated
by
cyclic
adenosine
monophosphate
(cAMP)
widely
seen
across
animals
thought
to
contribute
learning
memory.
Hippocampal
mossy
fiber-CA3
pyramidal
cell
synapses
have
been
used
as
model
because
robust
short-
long-term
forms.
Moreover,
direct
recordings
from
large
fiber
terminals
allow
one
dissect
mechanisms.
Recently,
super-resolution
microscopy
flash-and-freeze
electron
revealed
localizations
site
molecules
vesicles
during
at
nanoscale,
identifying
molecular
mechanisms
potentiation.
Incorporating
these
growing
knowledges,
we
try
present
plausible
underlying
cAMP-mediated
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 2, 2025
Abstract
At
presynaptic
active
zones
(AZs),
scaffold
proteins
are
critical
for
coordinating
synaptic
vesicle
release
and
forming
essential
nanoarchitectures.
However,
regulatory
principles
steering
AZ
assembly,
function,
plasticity
remain
insufficiently
understood.
We
here
identify
an
additional
Drosophila
protein,
“Blobby”,
proper
nano-organization.
Blobby
biochemically
associates
with
the
ELKS
family
protein
Bruchpilot
(BRP)
integrates
into
newly
AZs.
Loss
of
results
in
fewer
AZs
forming,
ectopic
accumulations
(“blobs”)
disrupts
nanoscale
architecture
BRP-AZ
scaffold.
Functionally,
blobby
mutants
show
diminished
evoked
currents
due
to
reduced
probability
functional
sites.
is
also
present
adult
brain
synapses,
post-developmental
knockdown
mushroom
body
impairs
olfactory
aversive
memory
consolidation.
Thus,
our
analysis
identifies
layer
regulation
developmental
assembly
but
AZ-mediated
controlling
behavior.
Learning & Memory,
Год журнала:
2024,
Номер
31(5), С. a053919 - a053919
Опубликована: Май 1, 2024
Animal
brains
need
to
store
information
construct
a
representation
of
their
environment.
Knowledge
what
happened
in
the
past
allows
both
vertebrates
and
invertebrates
predict
future
outcomes
by
recalling
previous
experience.
Although
invertebrate
vertebrate
share
common
principles
at
molecular,
cellular,
circuit-architectural
levels,
there
are
also
obvious
differences
as
exemplified
use
acetylcholine
versus
glutamate
considered
main
excitatory
neurotransmitters
respective
central
nervous
systems.
Nonetheless,
across
systems,
synaptic
plasticity
is
thought
be
substrate
for
memory
storage.
Therefore,
how
brain
circuits
contacts
change
following
learning
fundamental
interest
understanding
computations
tied
behavior
any
animal.
Recent
progress
has
been
made
such
plastic
changes
olfactory
associative
mushroom
bodies
(MBs)
Drosophila
.
A
current
framework
memory-guided
behavioral
selection
based
on
MB
skew
model,
which
antagonistic
pathways
selectively
changed
strength.
Here,
we
review
insights
into
dedicated
output
update
known
about
pre-
postsynaptic
compartments
neurons.
We
still
face
fundamental
gaps
in
understanding
how
molecular
plastic
changes
of
synapses
intersect
with
circuit
operation
to
define
behavioral
states.
Here,
we
show
that
an
antagonism
between
two
conserved
regulatory
proteins,
Spinophilin
(Spn)
and
Syd-1,
controls
presynaptic
long-term
plasticity
the
maintenance
olfactory
memories
Drosophila.
While
Spn
mutants
could
not
trigger
nanoscopic
active
zone
remodeling
under
homeostatic
challenge
failed
stably
potentiate
neurotransmitter
release,
concomitant
reduction
Syd-1
rescued
all
these
deficits.
The
Spn/Syd-1
converged
on
close
F-actin,
genetic
or
acute
pharmacological
depolymerization
F-actin
deficits
by
allowing
access
synaptic
vesicle
release
sites.
Within
intrinsic
mushroom
body
neurons,
specifically
controlled
memory
stabilization
but
initial
learning.
Thus,
this
evolutionarily
protein
complex
behaviorally
relevant
plasticity,
also
observed
mammalian
brain
enigmatic
concerning
its
mechanisms
relevance.
Learning & Memory,
Год журнала:
2024,
Номер
31(5), С. a054013 - a054013
Опубликована: Май 1, 2024
The
intricate
molecular
and
structural
sequences
guiding
the
formation
consolidation
of
memories
within
neuronal
circuits
remain
largely
elusive.
In
this
study,
we
investigate
roles
two
pivotal
presynaptic
regulators,
small
GTPase
Rab3,
enriched
at
synaptic
vesicles,
cell
adhesion
protein
Neurexin-1,
in
distinct
memory
phases
Drosophila
mushroom
body
Kenyon
cells.
Our
findings
suggest
that
both
proteins
play
crucial
memory-supporting
processes
terminal,
operating
plasticity
modules.
These
modules
likely
encompass
remodeling
maturation
existing
active
zones
(AZs),
as
well
new
AZs.
Cell Reports,
Год журнала:
2023,
Номер
42(8), С. 112974 - 112974
Опубликована: Авг. 1, 2023
Long-term
memory
(LTM)
requires
learning-induced
synthesis
of
new
proteins
allocated
to
specific
neurons
and
synapses
in
a
neural
circuit.
Not
all
learned
information,
however,
becomes
permanent
memory.
How
the
brain
gates
relevant
information
into
LTM
remains
unclear.
In
Drosophila
adults,
weak
learning
after
single
training
session
an
olfactory
aversive
task
typically
does
not
induce
protein-synthesis-dependent
LTM.
Instead,
strong
multiple
spaced
sessions
is
required.
Here,
we
report
that
pre-synaptic
active-zone
protein
cholinergic
signaling
from
early
α/β
subset
mushroom
body
(MB)
produce
downstream
inhibitory
effect
on
formation.
When
eliminated
these
neurons,
was
then
sufficient
form
This
bidirectional
circuit
mechanism
modulates
transition
between
distinct
phase
functions
different
subpopulations
MB