Brigidi II Flashcards
Spine length
Spines are typically
0.5 – 2 μm in length
spine density in CNS? In CA1?
Spines density along
dendrites is usually
1 – 10 per μm of length
along CNS neurons;
≈ 2 spines per μm along
CA1 pyramidal neurons
What is PSD and how much area does it cover?
The postsynaptic density (PSD) occupies ≈ 10% of spine surface area to position
glutamate receptors at the surface in apposition to presynaptic boutons;
The presence of the PSD is necessary for glutamatergic transmission
precursors to spines
Neurons in the developing
brain initially establish
filopodia from dendrites
as they begin to form
synapses; filopodia
lack a PSD and are
thought to function as
precursors for spines
What regulates spine formation?
Actin cytoskeleton regulates spine formation and development
Treatment of young neurons in culture (DIV 5) with Latrunculin A (F-actin de-
polymerizing drug) disrupts spine development from filopodia and destabilizes
nascent synapses
Treatment of mature neurons (DIV 14) has little effect on spine density
Filopodia development requires dynamic F-actin; mature spines are relatively stable
distinct pools of f-actin regulate sub-spine architecture
Filopodia – to – spine transition
Actin binding proteins regulate PSD recruitment
and spine morphogenesis
Recruitment of the actin side-binding protein Drebrin A is necessary for filopodium-to-
spine transition and PSD establishment.
how long are a majority of spines stable?
over multiple days – even a month or longer
what regulates mature spine morphology and which experimental technique was used to determine it?
Dynamic actin treadmilling regulates mature spine morphology
FRET used to visualize
dynamic actin filament
assembly (F-actin brings
G-actin monomers to
55 m-10 distance)
FRET signal efficiency
is enriched in spines
relative to the dendritic
shaft; F-actin dynamics
are highly localized
within spine heads
LTP stim induces actin polymerization in heads
Local synapse-specific compartment or expansion of PSD surface?
Spines provide a micro-
compartment for
segregating postsynaptic
signals.
Spines necks act as a
diffusional barrier that
localizes biochemical
signaling within a
spine’s volume.
Spines localize
electrical signals
generated by
action potentials or
synaptic inputs
Spine structure – function relationship
Spine volume, and head
width directly correlate with
AMPAR density at the
postsynaptic membrane
and evoked synaptic
responses.
Glutamate uncaging evokes
largest postsynaptic currents
in spines with greatest head
width and volume.
Neighboring spines exhibit
no synaptic response;
compartmentalization
LTP has what effect on spines?
causes new spines to appear and preexisting spines were enlarged
Structural plasticity of the synapse
LTP-induced spine enlargement is rapid and persistent
Chemically-induced LTP triggers spine enlargement and surface insertion
of transfected AMPAR subunits in CA1 neurons.
Spine enlargement precedes receptor insertion by several minutes
Are functional or structural changes
sufficient for synaptic plasticity?
Blue light activation of neurons
expressing PSD-95-Cry2 +
GluA1-CIB2 (AMPAR subunit)
enhances synapse strength,
similar to LTP.
(it’s the ampa receptors, not the enlargement)
Spines undergo two phases of activity-dependent enlargement:
transient (∆250% vol
for <10 min) and sustained (∆50% vol for hours);
RhoA necessary for transient phase,
Cdc42 necessary for sustained phase.
