"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.
When Penny tells Leonard he needs to be more assertive in making decisions for himself, he starts standing up to Sheldon over small things. His confidence makes him want to demand the university support his idea for a plasma physics project. He threatens to quit if the university refuses, alarming both Sheldon and Penny, who consider this to be a risky career move. Sheldon is conflicted on whether or not he is being selfish over Leonard's decision, but Amy suggests that the fact that he is worried over Leonard's motivation proves that he does care about him, which he acknowledges. President Seibert refuses the project, but in order not to lose Leonard, gives him co-leadership over a photon entanglement project, leaving Leonard proud of himself and Penny impressed. Meanwhile, Raj shows Anu his lab, and suggests one possible answer for something he's seen in space might be alien life. When someone mentions this at his observatory presentation, the scientific community starts mocking him as a conspiracy theorist. Raj points out scientists should consider all possibilities when seeking the truth, though this causes people to think he believes in the Loch Ness Monster.
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".
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Producers, writers and others, including recurring guest star Wil Wheaton, joined the festivities on set and — hardly a spoiler alert — more laughing, crying and hugging ensued. Lorre embraced a happy Parsons, then moved on to each cast member as if it were a reception line. Galecki shared long, emotional hugs with his colleagues. After trying to keep their emotions under control for so long, it was finally time to just let go.
After Sheldon reminds the guys about the time they mined Bitcoin without him, the guys go on a quest to find their suddenly valuable missing cryptocurrency. They realize the currency is on a laptop which Leonard gave to Penny when they dating, which she then gave to her ex-boyfriend Zack. After Leonard and Penny go to Zack's apartment, he shows them a seven-year-old video that Penny recorded on the laptop soon after she broke up with Leonard. Leonard is touched by the video which shows a drunk Penny lamenting the break-up of her relationship with him.