As your schemas sit on top of Mongoose, the only absolute is that they need to be defined after Mongoose is required. You don't need an active or open connection to define your schemas.

That being said it is advisable to make your connection early on, so that it is available as soon as possible, bearing in mind that remote database or replica sets may take longer to connect than your localhost development server.

While no action can be taken on the database through the schemas and models until the connection is open, Mongoose can buffer requests made from when the connection is defined. Mongoose models also rely on the connection being defined, so there's another reason to get the connection set up early in the code and then define the schemas and models.