We present principles for an integrated neuroinformatics framework which makes explicit how models are grounded on empirical evidence, explain (or not) existing empirical results and make testable predictions. The new ontological framework makes explicit how models bring together structural, functional, and related empirical observations. We emphasize schematics of the model’s operation linked to summaries of empirical data (SEDs) used in both the design and testing of the model, with tests comparing SEDs to summaries of simulation results (SSRs) from the model. We stress the importance of protocols for models as well as experiments. We complement the structural ontology of nested brain structures with a functional ontology of Brain Operating Principles (BOPs) for observed neural function and an ontological framework for grounding models in empirical data. We present an implementation of this ontological framework in the Brain Operation Database (BODB), an environment in which modelers and experimentalists can work together by making use of their shared empirical data, models and expertise.