It has been hypothesized that the direction of synaptic weight change
elicited by synaptic activity depends on the magnitude of the activity
-dependent rise in intracellular Ca2+ concentration. Several aspects o
f this hypothesis were examined at the Schaffer collateral CA1 synapse
, where both long-term depression (LTD) and long-term potentiation (LT
P) can be elicited and are Ca2+ dependent. Brief tetanic stimulation,
which normally generated LTP, could induce LTD when Ca2+ entry via NMD
A receptors was limited either by moderate concentrations of D-APV or
by voltage clamping cells at negative membrane potentials. Repetitive
activation of voltage-dependent Ca2+ channels in the absence of affere
nt stimulation could also elicit an LTD that was Ca2+ dependent and wa
s occluded by prior generation of homosynaptic LTD using prolonged low
frequency stimulation. These results provide strong evidence that the
minimal requirements for inducing LTD involve simply a transient infl
ux of Ca2+ into the postsynaptic cell, via either NMDA receptors or vo
ltage-dependent Ca2+ channels.