One of the recurring plot lines is the relationship between Leonard and Penny. Leonard becomes attracted to Penny in the pilot episode and his need to do favors for her is a frequent point of humor in the first season. Meanwhile, Penny dates a series of muscular, attractive, unintelligent, and insensitive jocks. Their first long-term relationship begins when Leonard returns from a three-month expedition to the North Pole in the season 3 premiere. However, when Leonard tells Penny that he loves her, she realizes she cannot say it back. Both Leonard and Penny go on to date other people; most notably with Leonard dating Raj's sister Priya for much of season 4. This relationship is jeopardized when Leonard comes to falsely believe that Raj has slept with Penny, and ultimately ends when Priya sleeps with a former boyfriend in "The Good Guy Fluctuation".
Professor Proton, Sheldon's favorite childhood show, is being rebooted. After unsuccessfully auditioning for the part, he goes to Wil Wheaton for acting tips for his second audition. However, Sheldon is later dismayed when Wil is offered the role instead. Talking it over with Arthur in his dreams, he is still upset to see his idol replaced and considers Wil an enemy again. Meanwhile, Howard gets a vasectomy while Bernadette is on bed rest. Penny offers to take care of Halley for them, but they insult her by expecting her to be irresponsible. Halley ends up saying her first word by calling Penny "Mama."

When Bernadette tells Howard that she is expecting again, he is once again floored with fear about raising another child, particularly when he learns it’s a boy. Howard, who isn't athletically inclined, worries he will not be able to relate to a son who might one day expect his dad to be the stereotypical father. Despite his best attempts to get out of it, Howard has a vasectomy to avoid any future surprises and is placed on bed rest, joining his pregnant wife at home.
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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