In order to find the neural basis of learning and memory, we need detailed information about the pattern of synaptic connections and how and under what conditions do they change. We also need a theoretical framework to guide the discovery of meaningful patterns and integration with other data from neuronal to behavioral levels. I propose to make quantitative measurements of the synaptic connectivity patterns directly from the intact brain of adult mice while plasticity in the cortical circuits is induced by behavioral paradigms. This is made possible by the combined use of 2-photon laser scanning microscopy and transgenic animals expressing EGFP. By taking repeated measurements of spine locations and volumes over days from the mouse barrel cortex, I will probe the dynamics of process of formation and elimination of spines. Synaptic strengths can also be deduced from spine volumes. By observing the time course of those processes and correlating them with neuronal morphology, location in the barrel map, and behavioral conditions, I will attempt to investigate issues concerning the input specificity of plasticity, homeostatic regulation of synapses, synaptic correlates of receptive field plasticity, and try to construct a theory of spine motility and relate it to the better studied plasticity in synaptic strengths.
