Journal Club
April 25th, 2012
Paper Layout
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Overview
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Quantal transmission of CA1 synapses
•
Properties of basal transmission:
– The GluR1 sub-unit in distance-dependent scaling
•
LTP and postsynaptic insertion of AMPA channels
•
LTP and presynaptic mode of vesicle release
•
LTP and changes in extrasynaptic GluR1 concentration
•
LTP affects synaptic growth and the probability of vesicle release
Overview
•
Model of distance-dependent scaling at partially silent distal and proximal
synapses
•
Model of early and late phases of LTP
Model of distance-dependent scaling at partially silent distal and proximal
synapses
Model of early and late phases of LTP
Paper Layout
•
Overview
•
Quantal transmission of CA1 synapses
•
Properties of basal transmission:
– The GluR1 sub-unit in distance-dependent scaling
•
LTP and postsynaptic insertion of AMPA channels
•
LTP and presynaptic mode of vesicle release
•
LTP and changes in extrasynaptic GluR1 concentration
•
LTP affects synaptic growth and the probability of vesicle release
Quantal transmission of CA1 synapses
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Quantal response does not mean opening of all channels at CA1 synapses
Quantal size is 10pA (22)
Single AMPA channels generate 0.5 -1 pA (23),
quantal response is generated by ~ 20 channels
Properties relevant to Quantal Transmission
• Fast rise time indicate that the subset of channels that open at the peak of the response are
localized in a hotspot (~100 nm radius) near the location at which the vesicle is re- leased
(Fig. 4, A2) (25).
• This hotspot represents a small fraction of large synapses, which can be up to 1 μm in
diameter (18). Only near the site of release is the cleft glutamate concentration in the
millimolar range that is required to effectively load the multiple glutamate binding sites on
the multimeric AMPARs.
• Synapse stained to reveal both presynaptic active zone and postsynaptic density shows
alignment of the edges of the two structures. [From (52)]
• Amplitude histograms of evoked responses (minimal stimulation) before LTP induction and
shortly afterward. There is reduction in failure probability and increase in quantal size.
Model of distance-dependent scaling at partially silent distal and proximal
synapses
Paper Layout
•
Overview
•
Quantal transmission of CA1 synapses
•
Properties of basal transmission:
– The GluR1 sub-unit in distance-dependent scaling
•
LTP and postsynaptic insertion of AMPA channels
•
LTP and presynaptic mode of vesicle release
•
LTP and changes in extrasynaptic GluR1 concentration
•
LTP affects synaptic growth and the probability of vesicle release
The GluR1 Subunit in Distance Dependent Scaling
C1) Current evoked by glutamate application to excised extrasynaptic membrane
is larger distally than proximally and is virtually abolished in the GluR1 knockout.
C2) mEPSC amplitude is normally higher distally
than proximally, but amplitudes become equal in the GluR1 knockout. [From (12)]
Paper Layout
•
Overview
•
Quantal transmission of CA1 synapses
•
Properties of basal transmission:
– The GluR1 sub-unit in distance-dependent scaling
•
LTP and postsynaptic insertion of AMPA channels
•
LTP and presynaptic mode of vesicle release
•
LTP and changes in extrasynaptic GluR1 concentration
•
LTP affects synaptic growth and the probability of vesicle release
LTP and postsynaptic insertion of AMPA channels
(C1) Noise analysis used to estimate number and conductance of AMPA
channels in the extrasynaptic membrane before LTP.
(C2) Same after LTP.
(D1 and D2) Summary data show that LTP produces an increase in channel
number but not in conductance. [From (50)]
Paper Layout
•
Overview
•
Quantal transmission of CA1 synapses
•
Properties of basal transmission:
– The GluR1 sub-unit in distance-dependent scaling
•
LTP and postsynaptic insertion of AMPA channels
•
LTP and presynaptic mode of vesicle release
•
LTP and changes in extrasynaptic GluR1 concentration
•
LTP affects synaptic growth and the probability of vesicle release
LTP and presynaptic mode of vesicle release
(A1) Before LTP induction, L-AP5 abolishes the NMDA EPSC, indicating low cleft
glutamate concentration.
(A2) LTP induced by a pairing protocol produces a very large increase in AMPA
current.
(A3) After LTP induction, the NMDA EPSC is no longer strongly inhibited by L-AP5,
suggesting the presence of a higher cleft glutamate concentration. [From (39)]
LTP and presynaptic mode of vesicle release
(C1) Direct measurement of vesicle release using activity-dependent destaining of
FM 1-43 shows faster destaining after LTP induction, indicating enhanced
probability of vesicle release. FM 1-43 labels synaptic vesicles.
(C2) Statistics before and after LTP induction or control. [From (57)]
Paper Layout
•
Overview
•
Quantal transmission of CA1 synapses
•
Properties of basal transmission:
– The GluR1 sub-unit in distance-dependent scaling
•
LTP and postsynaptic insertion of AMPA channels
•
LTP and presynaptic mode of vesicle release
•
LTP and changes in extrasynaptic GluR1 concentration
•
LTP affects synaptic growth and the probability of vesicle release
Model of distance-dependent scaling at partially silent distal and proximal
synapses
Model of early and late phases of LTP