The chapter discusses the role played by temporal covariance of pre- and post-synaptic activity in altering synaptic efficacy. This phenomenon is demonstrated in cells of the primary visual cortex in guinea-pigs and cats, and in more mature animals as well as those at the critical development age for the visual cortex. The results suggest that there is a temporal window about which the pre- and post-synaptic conjunction occurs in order to alter synaptic efficacy. This is particularly important if temporal associations are to be detected and specifically modify the connections that participated in them. The effects occur in the visual cortex beyond the classically defined critical period. The results also suggest that a threshold mechanism operates to only allow the effects of temporal conjunction of pre- and post-synaptic activity to occur outside of a certain “dead zone” around the resting membrane potential. The effects observed appeared to be spatially specific— that is, positive pairing (conjunction of pre-synaptic activation and post-synaptic depolarization) only enhances the efficacy of the paired synapses, and negative pairings (conjunction of pre-synaptic activation and postsynaptic hyper-polarization) only reduce the efficacy of the paired synapses. In some cases, unpaired pathways onto the same cell show no effect, or in other cases, the unpaired pathway shows an opposite effect. © 1993, Academic Press Inc.