What research won The Big Bang Theory's Amy Farrah Fowler the cover of Neuron?

Science featured in most TV shows is so ludicrously inaccurate that fact-checking it is no fun. It’s best to either avoid watching or to suspend disbelief. However, The Big Bang Theory is a pleasant exception. The show is set in present-day Pasadena, California, and follows the unlikely friendship of a waitress and aspiring actress Penny with several Caltech scientists. Most of the scientist characters are physicists, but as of Season 3, the show added a microbiologist character and a neurobiologist character. It’s a sitcom, and the laws of the genre require the characters to be more exaggerated caricatures than realistic personalities. But the cast member portraying the neurobiologist has a PhD in that field and the cast members portraying physicists are briefed on the current trends by a UCLA physics professor, so the science tends to be realistic. I am only on the fifth season out of seven, as I discovered the show last year, but I thought that it would be fun to translate what the show’s neurobiologist Amy Farrah Fowler says about her research into plain English. If you haven’t seen the first five seasons of the show and don’t want spoilers, please read no further.

            The twelfth episode of the fifth season provides the most detailed description of Amy’s research. In it, Amy is out on a dinner date with her physicist boyfriend Sheldon Cooper. Over drinks, she tells him that her “most recent paper on how cooperative long-term potentiation can map memory sequences in dendritic branches has made the cover of Neuron.” To a neurobiologist, that is of course splendid news. Not only did Amy’s research get published in a prestigious journal, but also the editors of that journal deemed it the most important of the issue and put it front and center on the cover. Sheldon, however, ignores this completely, switching the topic of conversation to the number of Twitter followers he has. The episode then goes on to make fun of Sheldon’s defects of character, and a non-specialist like me (I am working toward a PhD in cell biology, not neurobiology) is left wondering what Amy’s accomplishment actually is.

            The first hit from the Google search of the phrase “cooperative long-term potentiation can map memory sequences in dendritic branches” is a 2004 Trends in Neuroscience review article with it as the title. Already this is reassuring because scientific literature with this terminology exists. Using information from the review and from picking the brain of my Neuroblog editor Nick Weiler (whose PhD is in neurobiology), let’s unpack the phrase from the beginning.

            Long-term potentiation means that if one neuron fires a signal and makes another neuron it’s connected to fire a signal, then the connection between these two neurons will strengthen. Professor Carla Shatz at Stanford once summarized long-term potentiation as “the neurons that fire together, wire together.” This concept was introduced in 1949 by Donald O. Hebb and is fundamental to modern neurobiology. Cooperative long-term potentiation is an extension of this idea to weaker signals. Basically, if instead of sending a single strong signal to a neighbor, a neuron sends many weak signals, the weak signals will cooperate and the two neurons will still be able to achieve long-term potentiation. In the brain, most signals sent between neurons are weak, so cooperative long-term potentiation is more relevant to what happens in the human body.

            To map memory sequences means to translate a temporal order of events into a spatial order of connections between neurons. The idea of memory sequence could potentially explain how the human brain constructs memories. If the brain really does remember events and experiences by constructing connections between neurons, then, given how much we remember, it’s no wonder that the connections are so numerous and complex. How does the brain construct these connections? To answer that we need to define what dendritic branches are.

            Dendritic branches are extensions on the neuron where it receives signals. A neuron has many dendritic branches, grouped together into dendrites, where it receives signals and one axon, another type of extension, where it can send signals to other neurons. This diagram illustrates how axons connect to dendritic branches. Some scientists think that each connection between a dendritic branch and an axon encodes one memory, and the arrangement of dendritic branches in space encodes related memories. That’s why this arrangement is called memory sequence.

            The idea of memory sequence is controversial. There’s no way to measure what all the signals being received by a neuron mean. Therefore, at present it’s impossible to test directly whether the brain maps memories by connecting axons of neurons that generate related signals to dendritic branches close together on the neuron that receives these signals. But it’s an active area of research.

            Putting it all together, Amy works on how neurons firing together construct connections within the brain that may store memories. Of course, the phrase she utters does not describe her exact discovery, but her field is cool, and a breakthrough in it could certainly be Neuron-cover-worthy.