We strive to understand the role of hippocampus in memory formation by manipulating its functional elements, namely the assemblies of cells that carry out particular tasks. This objective raises four practical questions. How are such assemblies to be defined? How can they be accessed? How might their activity be perturbed? And how should the resulting change in the system be detected and evaluated? Hippocampal neurons are organized into three broad classes: excitatory, inhibitory and modulatory. In some cases, the classes can be subdivided further, on the basis of neurochemical markers, mainly calcium binding proteins and neurotransmitters. We work in mice, using these differences in the complement of expressed proteins to target specific cell populations. As an alternative, we are testing several new genetic approaches designed to identify and access neurons displaying heightened activity during memory tasks. Selected neurons are sensitized to subsequent manipulation using a variety of heterologous receptors and ion channels. We then evaluate the effects of cell-type specific optical or pharmacological perturbation on hippocampal circuit dynamics (electrophysiologically) and on animals memory functions (using behavioral assays).