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Dimitri Yatsenko began development of DataJoint in Andreas S.Tolias' lab in the Neuroscience Department at Baylor College of Medicine in the fall of 2009. Initially implemented as a thin MySQL API in MATLAB, it defined the major principles of the DataJoint model.

Many students and postdocs in the lab as well as collaborators and early adopters have contributed to the project. Jacob Reimer and Emmanouil Froudarakis became early adopters in Andreas Tolias' Lab and propelled development. Alexander S. Ecker, Philipp Berens, Andreas Hoenselaar, and R. James Cotton contributed to the formulation of the overall requirements for the data model and critical reviews of DataJoint development.

Outside the Tolias lab, the first labs to adopt DataJoint (approx. 2010) were the labs of Athanassios G. Siapas at CalTech, Laura Busse and Steffen Katzner at the University of Tübingen.

In 2015, the Python implementation gained momentum with Edgar Y. Walker and Fabian Sinz joining as principal contributors.

In 2016, Andreas Tolias Lab joined the MICrONS project, using DataJoint to process volumes of neurophysiology and neuroanatomical data shared across large teams.

In 2016, Vathes LLC was founded to provide support to groups using DataJoint.

In 2017, DARPA awarded a small-business innovation research grant to Vathes LLC (Contract D17PC00162) to further develop and publicize the DataJoint framework.

In June 2018, the Princeton Neuroscience Institute, under the leadership of Prof. Carlos Brody, began funding a project to generate a detailed DataJoint user manual.