BIPN 140: Cellular Neurobiology

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BIPN 140 Cellular Neurobiology LECTURE 11
Synaptic Plasticity I
Website http//www.biology.ucsd.edu/classes/bip
n140.FA07
INSTRUCTORS Nicholas C. Spitzer
(nspitzer_at_ucsd.edu) Darwin K. Berg
(dberg_at_ucsd.edu)
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Fig 8.1a Forms of short-term synaptic
plasticity synaptic facilitation
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Fig 8.1b Dependence of facilitation on spike
interval
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Fig 8.1c Synaptic depression augmentation
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Fig 8.1d Dependence of synaptic depression on
prior transmitter release
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Fig 8.1e Postsynaptic Potentiation (PTP)
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Fig 8.2 Short-term plasticity at the NMJ
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Fig 8.6 The rodent hippocampus
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Fig 8.7a Long-term potentiation of Schaffer
collateral-CA1 synapses
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Fig 8.7b LTP of Schaffer collateral-CA1 synapses
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Fig 8.7c LTP of Schaffer collateral-CA1 synapses
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Fig 8.7d LTP of Schaffer collateral-CA1 synapses
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Fig 8.8 Pairing presynaptic and postsynaptic
activity causes LTP
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Fig 8.9 LTP at a CA1 pyramidal neuron receiving
inputs from two independent pathways
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Fig 8.10 The NMDA receptor channel can open only
during depolarization
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Fig 8.11 Signaling mechanisms underlying LTP
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Synaptic Tagging and Long-Term Potentiation by U
Frey GM Morris
Nature 385533-536 (1997)
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BACKGROUND The early phase of LTP (lt 3 hrs)
does not require protein synthesis whereas the
late phase (gt 3 hrs) does. If protein synthesis
occurs at least in part in the cell body, how
does the cell know which synapses should receive
the proteins to sustain late-phase LTP? Frey
Morris propose that induction of early-LTP
confers a tag on the synapse such that it now
is uniquely able to receive the components
produced by protein synthesis. The tag is lost
within 3 hrs, defining a window of opportunity
for acquistion of late-LTP.
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EXPERIMENT They separately stimulate 2 sets of
synapses, varying the intensity, timing, and
blockade of protein synthesis to determine what
conditions are required for late-phase LTP. A
weak tetanus induces early- but not late-phase
LTP (requires protein synthesis). A strong
tetanus does. A weak tetanus can induce
late-LTP, however, if a strong tetanus is given
at the same time to another synapse on the
cell. What happens if the strong tetanus precedes
the weak tetanus, and the latter is given when
protein synthesis is blocked? Can proteins
recently made in response to the initial tetanus
now be recruited by the second population of
stimulated synapses?
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Fig. 2a-b (control) Tetanic stim of S1 induces
S1 late-phase LTP without affecting S2
A Arrangement of stimulating and recording
electrodes in CA1 B Tetantic stimulation of
S1 produced long-lasting LTP in S1 but no effect
on EPSP amplitude in S2 as monitored by field
potential recordings.
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Fig. 2c (control) Neither tetanic stim of S1 or
S2 yields late-phase LTP if protein synthesis is
blocked.
Fig. 2d (exptl) Stim of S2 generates late-phase
LTP even if protein syn is blocked, providing
that a preceding stim of S1 occurred within 1-2
hrs and protein syn was allowed then.
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Fig. 2e (control) If the S2 population was
surgically isolated from the stimulated S1
population, then it could not display late-phase
LTP when following the previous protocol (as in
fig 2c/d)
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RESULTS Weak tetanic stimulus of S2 generated
late-LTP providing that a conditioning strong
tetanic stimulus was delivered to other synapses
(S1) on the neuron. Under these conditions S2
could acquire (protein-synthesis-dependent)
late-LTP even though protein synthesis was
blocked during S2 stimulation (but not if it was
also blocked during S1 stim or if one waited more
than 1-2 hrs) TAKEHOME Weak tetanic
stimulation is sufficient to tag the S2
synapses such that they can hijack proteins being
synthesized for LTP under the earlier direction
of input from S1. Implies a tag being assigned
to relevant synapses.