The Zazzy Substitution (2010)

Sheldon and Amy Farrah Fowler are very compatible with each other, as evidenced by how well they can play "counter-factuals", a game they invented requiring them to know what the other is thinking would be the answer to a question about "an alternate world that differs from ours in one key aspect" . Bringing Amy into the group is a source of consternation, as the guys can barely handle Sheldon by himself, let alone with Amy, his female equivalent. At one lunch, Amy belittles Sheldon's occupation as a theoretical physicist relative to, in her opinion, her more superior occupation of neurobiologist. This leads Sheldon to propose for the "relationship terminate immediately", much to the delight of the other guys. As a result of the breakup, Sheldon becomes more peculiar than his normal self, and adopts a cat as a substitute for Amy. This one cat quickly grows into a collection of 25 cats. This worries Leonard, who calls Sheldon's mother to come for help. When she arrives, Mrs. Cooper is shocked, as she never expected this, so she calls Amy to come and help. Amy agrees out of scientific curiosity, because since Mrs. Cooper told her that Sheldon is losing his mind over Amy, as a neurobiologist, Amy wants to see how someone can lose their mind. As Amy, Sheldon, Leonard, and Sheldon's mother sit around the living room, Sheldon's mother employs a technique of reverse psychology which Leonard instantly picks up on, but Sheldon is completely oblivious to. She tells Sheldon that it was a good thing he and Amy broke up because they are completely incompatible. Sheldon is instantly offended, so to prove his mother wrong, he offers Amy to reconcile, which she agrees after a negotiation on the amount of responsibility Sheldon has to accept for the breakup (Amy offered 80%, Sheldon countered with 40%, settling at 65%). The episode ends with Sheldon and Amy giving $20 to anybody willing to adopt a cat.

Recurring characters: Mayim Bialik as Amy Farrah Fowler and Laurie Metcalf as Mrs. Cooper.

Title reference: Sheldon describes one of his cats as being very "zazzy".