In scenes set at Howard's home, he interacts with his rarely-seen mother (voiced by Carol Ann Susi until her death) by shouting from room to room in the house. She similarly interacts with other characters in this manner.[85] She reflects the Jewish mother stereotype in some ways, such as being overly controlling of Howard's adult life and sometimes trying to make him feel guilty about causing her trouble. She is dependent on Howard, as she requires him to help her with her wig and makeup in the morning. Howard, in turn, is attached to his mother to the point where she still cuts his meat for him, takes him to the dentist, does his laundry and "grounds" him when he returns home after briefly moving out.[86] Until Howard's marriage to Bernadette in the fifth-season finale, Howard's former living situation led Leonard's psychiatrist mother to speculate that he may suffer from some type of pathology,[87] and Sheldon to refer to their relationship as Oedipal.[88] In season 8, Howard's mother dies in her sleep while in Florida, which devastates Howard and Stuart, who briefly lived with Mrs. Wolowitz.

As the theme of the show revolves around science, many distinguished and high-profile scientists have appeared as guest stars on the show. Famous astrophysicist and Nobel laureate George Smoot had a cameo appearance in the second season.[56] Theoretical physicist Brian Greene appeared in the fourth season, as well as astrophysicist, science populizer, and physics outreach specialist Neil deGrasse Tyson, who also appeared in the twelfth season.
The first and second seasons were only available on DVD at their time of release in 2008[197] and 2009.[198] Starting with the release of the third season in 2010[199] and continuing every year with every new season, a Blu-ray disc set has also been released in conjunction with the DVD. In 2012, Warner Bros. released the first two seasons on Blu-ray,[200] marking the first time that all episodes were available on the Blu-ray disc format.

As the theme of the show revolves around science, many distinguished and high-profile scientists have appeared as guest stars on the show. Famous astrophysicist and Nobel laureate George Smoot had a cameo appearance in the second season.[56] Theoretical physicist Brian Greene appeared in the fourth season, as well as astrophysicist, science populizer, and physics outreach specialist Neil deGrasse Tyson, who also appeared in the twelfth season.
Sheldon and Amy are surprised to find that Wil Wheaton's new Professor Proton show is actually very entertaining and that Wil had Howard on as a guest. On Howard's suggestion, Sheldon apologizes to Wil, mending their friendship, and tells him he wants to be on the show; but Wil asks for Amy. Sheldon tells her to do it, but she says she often doesn't do things to avoid upsetting him. Sheldon is horrified when he realises how selfish he has been, especially when he finds out that the men do the same for him. Sheldon encourages Amy to go on the show to inspire girls to pursue science while trying to control his obvious jealousy for her. Meanwhile, Leonard writes a book about a physicist that solves a murder, the protagonist Logan Dean is based on himself. Bernadette points out Logan's mean boss Illsa is similar to Penny, who thinks it is based on Bernadette, though Leonard does not correct her. However, Bernadette tells Penny the truth, upsetting her and making her mad at Leonard. After calling his mother for advice, Leonard learns that Illsa is actually like her; but abandons the book when he realizes he wrote romantic tension into the relationship between the characters.

Wil Wheaton brings William Shatner on his Professor Proton show to meet Sheldon, who gets so excited that he vomits on Shatner. Going to Wil to apologize, he finds Wil hosts a Dungeons & Dragons group with his celebrity friends including Shatner. Finding out Stuart is in the group and never told them, the guys make Stuart panic and quit. Wil secretly invites Leonard who discovers that the group also includes Shatner, Kevin Smith, Joe Manganiello and Kareem Abdul-Jabbar. Leonard tells Penny, who tells Amy and Bernadette, all three women having a crush on Manganiello. Because of that indiscretion, Wil kicks out Leonard and admonishes the guys for using him for his connections, and says that one of the worst things about being a celebrity is not knowing whether someone will like him for himself. To apologize, the guys invite Wil to play D&D with them at Leonard’s apartment, but Wil, secretly in the middle of a game with Penny, Amy and Bernadette and the group, politely turns them down, before allowing the girls to send them a photo of the events as payback.
Sheldon and Amy go on their honeymoon to New York City, starting with Legoland New York. Sheldon's insistence on scheduling their marital relations stresses Amy. He says he only does it to remind himself to be intimate with her. They compromise by letting him make a schedule without sharing it with her. Leonard and Penny discover Mr. Larry Fowler (Teller) in Sheldon and Amy's apartment hiding from his wife (Kathy Bates). Leonard notices parallels in his own marriage, which offends Penny. Leonard apologizes, and Penny convinces Mrs. Fowler to give her husband a break. When Mrs. Fowler wants to hang out with her regularly, Penny scares Larry out of the building. Raj instigates a Twitter feud with Neil deGrasse Tyson but is scared off when confronted over the phone. Neil then calls Bill Nye to scare him, too.
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.

Sheldon cannot find the perfect wedding date and begins talking in his sleep, adopting the persona of a laid-back person who goes with the flow. Amy and Penny believe that his subconscious mind is trying to tell him to be more relaxed; his attempt to be so while wearing flip-flops ends in disaster. He decides to leave all the wedding planning to Amy while he wears a Star Trek uniform underneath his tuxedo. Meanwhile, Raj and Stuart both become interested in Bernadette's new coworker Ruchi. While she likes them both as friends, she does not want a relationship with anyone.
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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