Understanding the synaptic and molecular basis for learning and memory in the neocortex depends upon a clear understanding of the anatomical and connectional diversity within this structure. To the extent that different types of synapses within the neocortex have distinct electrophysiological and, thus, molecular properties, the types of plasticity that these synapses manifest may also be distinct. If thresholds for plasticity are different for excitatory synapses onto inhibitory neurons than for excitatory synapses onto excitatory neurons, the same pattern of excitatory presynaptic activity will have difference consequences on excitatory and inhibitory networks. Differential plasticity will thus affect the way in which experience can modify sensory maps in the neocortex. Experimental support for this hypothesis is presented, as well as some predictions about the function of different types of neocortical pathways and plasticity.