My main interests are: Elucidating the a) input/output properties of neurons and b) the structure and function of dendritic spines and their role in information processing and plasticity of cortical circuits. In neocortex, as well as many other brain areas, excitatory inputs terminate on dendritic spines. Despite their evident importance, the function of spines is not completely understood. Their peculiar morphology, with a small head separated from the main dendrite by a spine neck, may be responsible for enabling the biochemical isolation of inputs, which in turn can allow different forms of synaptic plasticity, such as LTP. Indeed there is a wealth of information in support of the biochemical isolation of inputs, yet many basic questions regarding the function of dendritic spines in information processing and storage in the intact brain remain unknown. Can spines behave as electrical compartments? If so, what is their role? Are spines plastic structures that can modify their structure and thus the cortical circuit? Although in vitro studies have added significantly to our understanding of the role of spines, it is evident that our understanding of their role in an intact brain is unknown. Since most excitatory inputs occur on spines, the understanding of their function will be a major contribution to a fundamental question of Neuroscience: how does a neuron integrate the thousands of inputs it receives to produce an appropriate response? Thus, my goal will be to study the input/output properties of pyramidal cells in physiological and pathological in in vitro and in vivo models, with an emphasis on dendritic spines. Implicit in this is gaining an understanding of how synaptic plasticity at spines affects the integrative properties of neurons. I will take a multifaceted approach to answering these questions, using optical, electrophysiological, structural, and molecular tools.