生物物理学 II Handout No. 8①②
Figure63-11 Maintenance of theearly phase of LTP in the CA1
region of the hippocampus depends on an increase in presynaptic transmitter release.
Quantal analysis of LTP in area
CA1 is based on a coefficient ofvariation of evoked responses.
This analysis assumes that thenumber of quanta of transmitter
released follows a binomialdistribution, where the coefficientof variation (mean squared/variance) provides an index oftransmitter release from thepresynaptic terminal that isindependent of quanta) size.
(From Malinow and Tsien 1990.)
A. With LTP the ratio of meansquared to variance increases,indicating an increase in transmitter release. This increase
occurs only in the pathway that ispaired with depolarization of thepostsynaptic cell. It does notoccur in a control pathway that is
not paired.
B. At normal rates of stimulation
the number of failures in transmission is significant (60%). After
LTP the percentage of failuresdecreases to 20%, another indication that LTP is presynaptic.

③Figure 63-12 The early and late phases of LTP are evident in thesynaptic trans- mission between a single CA3 cell and a single Catcell. (From Bolshakov et al. 1997.)
A. A single CA3 cell can be stimulated selectively to produce a single
elemen- tary synaptic potential in a CA1 cell. When the CA3 cell isstimulated repeat- edly at low frequency, it gives rise to either anelementary response of the size of a miniature synaptic potential or afailure.
B. In control cells there are many fail- ures; the synapse has a low
probability of releasing vesicles. The distribution of the amplitudes of many
responses can be approximated by two Gaussian curves, one centered onzero (the fail- ures) and the other centered on 4 pA (the successfulresponses). These histo- grams are consistent with the type of synapse
illustrated here, in which a sin- gle CA3 cell makes a single connection ona CA1 cell. This connection has a single active zone from which it releases
a single vesicle in an all-or-none manner (failures or successes).
C. With the early phase of LTP the prob- ability of release rises
significantly, but the two Gaussian curves in the distri- bution of responses
is consistent with the view that a single release site still releases only avesicle but now with a high probability of release.
D. When the late phase of LTP is in- duced by a cAMP analog(Sp-cAMPS), the distribution of responses no longer fits two Gaussian
curves but instead requires three or four Gaussian curves, suggesting thepossibility that new pre- synaptic active zones and post-synaptic receptors
have grown. These effects are blocked by anisomycin, an inhibitor ofprotein synthesis.

Figure 63-13 A model for the early and late phase of LTP. A single
train of action potentials leads to early LTP by activating NMDA receptors,
Ca2+ influx into the postsynaptic cell, and a set of second messengers.
With repeated trains the Ca 2+ influx also recruits an adenylyl cyclase,which activates the cAMP-dependent protein kinase (cAMP kinase)leading to its translocation to the nucleus, where it phosphorylates theCREB protein. CREB in turn activates targets that are thought to lead tostructural changes. Mutations in mice that block PKA or CREB reduce or
eliminate the late phase of LTP. The adenylyl cyclase can also bemodulated by dopaminergic and perhaps other modulatory inputs. BDNF =brain-derived neurotrophic factor; C/EBPb = transcription factor; P =phosphate; R(AB) dominant negative PKA; tPA = tissue plasminogenactivator.