Sunday, August 4, 2013

The Pensieve

Aficionados of the Harry Potter series of books will recall the pensieve, the physical receptacle of memories, that sits in Professor Dumbledore's office, with silvery memories darting around on a smoky background, like koi fish in a pond, ready to be plucked out at will, or locked away. However, in our every day unmagical Muggle world, neuroscientists have long grappled with the question of the existence of a physical location of memories, and even more intriguingly with the basis of false memory, viz. the remembrance of incidents that never occurred. In a series of important papers, the most recent of which was published in the 25th July issue of Science, a group of scientists at the RIKEN-MIT Center for Neural Circuit Genetics, have established the existence of networks of neurons that form memory traces (or emgrams) for each experience we have, succeeded in activating them via optical techniques, and also in implanting memory associations of incidents that never occurred.

Early research in neuroscience in the 1940-s suggested that episodic memories were stored in the hippocampus, an area of the temporal lobe of the brain. Electrical stimulation of the hippocampus, undertaken in the treatment of epileptic seizures, succeeded in triggering episodic memories. However, it was not established that the memory traces were stored in specific cells of the brain. To establish this required new techniques, called optogenetic techniques. In a study carried out by Susumu Tonegawa and coworkers at MIT, mouse hippocampal cells were engineered to express the gene for channelrhodopsin, a protein that activates neurons when simulated by light.  They also modified the gene so that channelrhodopsin would be produced whenever the c-fos gene, necessary for memory formation, was turned on. Last year, the researchers conditioned these mice to fear a particular chamber by delivering a mild electric shock (yes, the cells were in live mice. Neuroscience experiments aren't pretty!). As the memory was formed both the c-fos gene and the engineered channelrhodopsin gene was switched on. Thus, the cells encoding the memory (located in an area called the Dentate Gyrus of the hippocampus) were tagged with the light sensitive protein. When the mice were put in a different chamber, they behaved normally. However, when a light pulse was delivered to the hippocampus, stimulating the optically tagged memory cells, the mice froze in fear as the memory of the shock was activated. Thus a direct contact was established between the memory trace and its storage location.

This was remarkable  in itself, but then the researchers went further. They tried to implant false memories in the mices' brains. First, the mice were allowed to explore a chamber, chamber A where no shocks were given. However, their memory cells were labelled with the optically sensitive gene. The next day, the mice were put in chamber B, where a mild shock was delivered, and simultaneously, the cells encoding the memory trace of chamber A were switched on optically. The third day, the mice were put in chamber A, where they froze in fear, even though they had never been shocked in chamber A. A false memory had been implanted (`incepted'). The mice feared chamber A, because when they were given the shock in chamber B, they were reliving the memory of being in chamber A. The mice also retained the fear of chamber B, where the real shock was given. However, they were not as fearful as those mice who had recieved a shock in chamber B, without having a memory of chamber A activated. A similar result had been achieved by Mark Mayford and coworkers at the Scripps Institute in San Diego, last year, using drug induced stimuli.

Now that we have seen the inception of false memories, what next? Steve Ramirez, who is one of the authors of the Science paper, said, `Now that we can reactivate and change the contents of memories in the brain, we can begin asking questions that were once the realm of philosophy. Are there multiple conditions that lead to the formation of false memories? Can false memories for both pleasurable and aversive events be artificially created? What about false memories for more than just contexts — false memories for objects, food or other mice? These are the once seemingly sci-fi questions that can now be experimentally tackled in the lab.'

It is clear that this line of research opens up a whole new area of brain and memory research, and also has implications for legal and ethical issues. Here comes the brave new world! Let's see how it all turns out.

This blog post is by Neelima Gupte and Sumathi Rao.


AmOK said...

Yes. Eventually marketing can be done via such a linkage obviating the need for repetitive TV commercials.

Neelima said...

Those would be the more harmless uses!