The science of "Eternal Sunshine of the Spotless Mind"

Optogenetics has revolutionized neuroscience. For those of us scouring neuroscience headlines, the word "channelrhodopsin" is the Facebook clickbait equivalent of "You'll never believe what happens next!!" But aren't we are all fascinated by the ability to activate a cell by flashing light on it?

From a physiological standpoint, they are useful as tools for dissecting out cell networks and for figuring out the nature of how cells communicate with each other. As a scientist, this IS the very immediate goal of developing these optogenetic strategies. But translating an optogenetic study into a behavioral correlate is the long term objective for bringing these findings into clinical therapy. One day, this technique might turn "science fiction" into just "science."

Eternal Sunshine as a neuroscience lesson

Eternal Sunshine of the Spotless Mind fits that small niche genre of "rom-dram-sci-fi-psychological thriller," with surprisingly wide appeal. It tells the story of a couple who undergo a procedure to erase memories of each other after their relationship falls apart. By means of a magical upside down colander, Jim Carrey's memories of his girlfriend slowly disappear. But in his mind, upon realizing he doesn't ever want to completely forget about her, he struggles to hold onto these memories by means of hiding her from the omnipresent neural eraser. 

A study published in Nature called "Labelling and optical erasure of synaptic memory traces in the motor cortex." is a start at bringing Eternal Sunshine into the real world. 

As described in the paper, Hayashi-Takagi and crew developed a unique light sensitive viral construct that specifically inserts itself into small protrusions of dendrites. These protrusions, called spines, are thought to be one of the places where memories are maintained. As the current train of thought goes, changes in the spines represent a form of learning, a semi-permanent change that results in a strengthening or weakening of a synaptic connection. Collectively, these changes are believed to explain how the brain is capable of storing memories. This study lends support in favor of this hypothesis.

Activation of Rac1 results in spine shrinkage due to intracellular mechanisms. Hayashi-Takagi's group uses the light sensitive form of Rac1 in order to exert temporal control over their activation, resulting in spine shrinkage upon exposure to a specific wavelength of light. Essentially, their experiments allow them to change the shape of spines with the flick of a light switch. So, according to their hypothesis, if their subjects were to learn a task, resulting in a change in spines that represents the site of learning, shining the light could potentially reverse any spine plasticity and therefore, "erase" the associated learned behaviors. In their hands, activating Rac1 resulted in a reversal of a learned performance task on an accelerating motorod, a standard behavioral test for assaying locomotor skills. 

These people deleted a motor memory.

Eternal Sunshine this is not, however. I believe there must be significant differences between the different types of memory - Motor memory, discrete memories, emotional memories, short term memories, etc. In my opinion, simple motor memories have simple sites for the memory to be stored, probably at several synapses in the primary motor cortex (which they specifically target in the study.) Other memories, like those complex, emotionally heavy memories depicted in Eternal Sunshine, are probably stored all over the brain rather than in one simple location. To some degree, the film might depict what happens in a real human brain during the formation of emotional memories. Jim Carrey runs around his consciousness trying to save Clementine from being erased. As we relive parts of their relationship, we see many areas of the brain that may experience changes during the complex emotions associated with love: Reward circuitry being activated (ventral tegmental area and the nucleus accumbens), fear and panic (amygdala), brief moments of rationality (prefrontal cortex), etc.

Hayashi-Takagi et al have shown interesting results with their study, and may have taken one giant step towards making Eternal Sunshine become a reality of the future.