One of the most fundamental properties of the brain is its ability to adapt rapidly to environmental changes. This is achieved mainly by changes in the connectivity between individual nerve cells. Synapses can be modulated in their strength by a variety of different mechanisms. We have investigated a number of these mechanisms, ranging from homeostatic control of synaptic efficacy to morphological manifestations of synaptic strengthening or weakening, and the role of calcium in these processes. Yet, while we are beginning to understand the cellular mechanisms underlying synaptic changes, it is important to consider the functional implications of synaptic plasticity in the intact brain. We are therefore applying new imaging methods to investigate the effects of experience on synaptic changes in cortical circuits. In particular, in vivo two-photon microscopy has enabled us to study morphological as well as functional plasticity at the level of individual neurons in the neocortex. These experiments are beginning to close the gap between traditional cellular and systems studies, and they will enable us to obtain a much more comprehensive understanding of the phenomenon of synaptic plasticity and its role in cortical function and ultimately behavior.