We have investigated the characteristics and mechanism of activity-dep
endent decreases in synaptic effectiveness in visual cortex. Repetitiv
e, low-frequency stimulation (LFS) of either layer IV or the white mat
ter of visual cortical slices was shown to result in a long-term depre
ssion (LTD) of intra- and extracellularly recorded synaptic responses
in layer III. In preparations in which responses to stimulation of two
independent pathways could be monitored, LFS of one pathway produced
LTD of responses to test stimulation of that input only, showing that
this form of LTD is homosynaptic. This form of LTD was dependent on th
e frequency and/or pattern of conditioning stimulation and on activati
on of NMDA receptors. Okadaic acid, an inhibitor of protein phosphatas
es 1 and 2a, inhibited LTD, but had no effect on induction of long-ter
m potentiation. In all of these respects, LFS-induced LTD in visual co
rtex closely resembles what has been recently documented in hippocampu
s. The combined data support a model in which LTD is triggered by a mo
dest elevation in postsynaptic Ca2+ and activation of protein-serine,
threonine phosphatases.