Backbone does not explicitly handle cleaning up objects for you. It's 50/50 you and the JavaScript runtime.
JavaScript is a garbage collected language like Java, C#, Ruby, and others. The basic of a garbage collected languages is that an object that is still referenced by your application will not be cleaned up. The counter to that is when an object is no longer referenced by your application, will be cleaned up.
JavaScript in general:
When you create a variable, you can either scope that variable to a local function or as a global variable.
Global variables are never cleaned up by the garbage collector, during the life of the page. The only time they are cleaned up is when you leave the HTML page behind entirely - navigate to a different page and force the browser to load the new page from the server (doing a complete server refresh) or closing the browser or browser tab.
Function scoped variables are cleaned up when the variable falls out of scope - that is, when the function has exited and there are no more references to it. There are a few exceptions to this: return values and closures.
A return value is held in your app by assigning the return value to another variable. A return value falls under the same general rules, but the variable is now in a different function. Once that variable goes out of scope, it can be cleaned up.
A closure allows a parent scope to provide values that a descendant scope can access. When the descendant scope is cleaned up, the parent's closured variable may be allowed to be cleaned up (assuming nothing else is holding on to it).
Objects with attributes and functions fall under the same rules. An object can reference another object or function by having an attribute assigned to it: myObj.foo = thatObj.
The DOM (Document Object Model - the HTML in your app) is a JavaScript object. Events and other references to your DOM work the same as any other reference. If you have an object handling a DOM event, it has a reference in your app and it won't be cleaned up by the garbage collector. If you want it cleaned up, you have to remove all references to it - including the DOM reference from the event handler.
Cleaning Up Memory
The general rule is that if you are loading data in to a backbone collection or object and you want that object to be cleaned up so it's not using anymore memory, you must remove all references to that object. This is just the standard JavaScript garbage collection rule.
You cannot force garbage collection, but you can force a variable to de-reference the thing it points to using the delete keyword in JavaScript: delete myVar
Backbone
Backbone is JavaScript so it falls under the same rules. There are some interesting uses of closures and references in Backbone that you need to be aware of, which will help you to know when you need to manually clean up some objects.
For example: events. An even handler / callback method works by having a reference between the object that triggers the event and the callback that handles the event. This is one of the easiest places to cause memory leaks in a Backbone app and I discuss it in detail, here: http://lostechies.com/derickbailey/2011/09/15/zombies-run-managing-page-transitions-in-backbone-apps/
Other than being aware of how events work in terms of references, just follow the standard rules for manage memory in JavaScript and you'll be fine. Once you remove all references to that collection of User objects, they'll be cleaned up.
