Leonard's mother Beverly visits, and he is thrilled when she takes an interest in his work. However, when he learns that she is doing research on him for a new parenting book, he is furious. He prepares to tell her how she let him down over the years, but instead chooses to accept and forgive her, and forgive himself for holding onto that resentment for so long. Beverley is touched that he forgave her and they share a genuine hug. Meanwhile, Anu gets a job offer in London. Raj prepares to fly out and propose to her, ready to follow her if she accepts. Howard stops Raj at the airport, saying there is a better match out there for him, convincing Raj to return home. Stuart and Denise are bothered by her creepy roommate Mitch, while Bernadette and Howard are tired of Denise constantly staying overnight with Stuart at their house. Stuart says he is ready to move in with Denise, and they say they love each other while convincing Mitch to move out.
Anu wants to have sex with Raj, but he gets so nervous in the leadup, that his selective mutism returns. Confessing to her, she is very understanding, revealing an unusual secret of her own. The next morning, he is able to have sex with her in the shower. Sheldon attempts to bond with his father-in-law, but Larry is more impressed with Howard's magic tricks, causing a jealous Sheldon to spend time with Mrs. Fowler. They bond after finding out Amy has been using Sheldon as an excuse to avoid her mother, though he does gently advise her to forgive her daughter like he would his wife. A remorseful Amy invites the Fowlers over for thanksgiving, where Sheldon and Mrs. Fowler continue to bond over Larry's ineptitude with magic.
"The Locomotive Manipulation" is the first episode in which Sheldon initiates a kiss with Amy. Although initially done in a fit of sarcasm, he discovers that he enjoys the feeling. Consequently, Sheldon slowly starts to open up over the rest of the season, and starts a more intimate relationship with Amy. However, in the season finale, Sheldon leaves temporarily to cope with several changes and Amy becomes distraught. However, in "The Prom Equivalency", he hides in his room to avoid going to a mock prom reenactment with her. In the resulting stand-off, Amy is about to confess that she loves Sheldon, but he surprises her by saying that he loves her too. This prompts Amy to have a panic attack.
Leonard and Sheldon are brilliant physicists—geniuses in the laboratory but socially challenged everywhere else. Enter beautiful, street-smart neighbor Penny, who aims to teach them a thing or two about life. Despite their on-again, off-again relationship in the past, Leonard and Penny have finally gotten married. Even Sheldon has found a female companion, entering into a "relationship agreement" with neurobiologist Amy Farrah Fowler, and he recently took their relationship to the next level by marrying her after a long courtship. In their free time, Leonard and Sheldon enjoy fantasy role-playing games with their ever-expanding universe of friends, including fellow scientists Koothrappali, Wolowitz, and Wolowitz’s adorable microbiologist wife, Bernadette, who is adjusting to life with their two children.

Sheldon needs half a billion dollars to prove his latest concept of string theory, which the University cannot afford to fund. Crowdfunding and selling some of his most valuable comic books to Stuart give him a small start. When Raj mentions gambling in Las Vegas, Sheldon goes there but is caught calculating odds by security before he can make any bets. Meanwhile, Amy takes Penny and Bernadette shopping for her wedding dress. She loves an old-fashioned one that the other girls admit that they find ugly, though Penny assures Amy she can make her own decisions about her wedding. Sheldon, however, comes home and sees Amy in the dress and loves how she looks.

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