30 October 2014

How do we know where is what? The ‘inner GPS’ in our brains

Identification of each location-specific place cell and the map built up by them was a major starting point in neural mapping

How do we know where is what? Recognize places and directions? Where do we store such information and recall them from memory? Today, thanks to the power of information technology, speedy computation and communication, we no longer need to ask a passer-by where a given place is, but use a Google Map on geographic positioning system (GPS). But how does the brain do all this? Animals such as rats or dogs, or even we humans before the computer age, did not have this facility and yet we carried on quite well. We stored such information in our brains and recalled them when needed. How does all this happen? Where is this ‘inner GPS’ in our brain?
Answers to some of these questions have come from the study of three scientists — John O’Keefe at the University College London, UK, May-Britt Moser and her husband Edvard Moser, both from Trondheim Norway — the trio whom were awarded the 2014 Nobel Prize in Physiology or Medicine.
It had been known for some time that the brain’s memory centre is the hippocampus, a seahorse shaped component (hippo means horse and kampus a sea monster, hence the name) lying below the cerebral cortex. It was in the late 1960s that John O’Keefe began working in the area of how the brain controls behaviour and how rats learn to navigate across a maze in a room. He placed rats in a large cage, stuck electrodes in chosen parts of their brain, notably the hippocampus and recorded the electrical signals coming out as the rats moved across space. When a rat goes to a particular place in the cage (say a corner or a bump), certain specific nerve cells were found to be activated. When it went to another location, yet another set of cells were activated. Gradually then, O’Keefe could identify what he termed as location-specific ‘place cells’ and a map built up by such place cells in the hippocampus, each place cell activated in a specific location or environment. This was a major starting point in neural mapping.
It was during this time that the Norwegian couple May-Britt and Edvard Moser finished their PhD degrees from the University of Oslo and went first to the University of Edinburgh and then to the O’Keefe lab at London as postdoctoral fellows to be mentored by him. Here they decided to take further neurophysiology of the inner GPS in rats. Upon winning a competitive research grant from the Kavli Foundation at California, U.S., they returned to Norway to set up a research centre at Trondheim. Their aim was to find out where the signals for the firing of the place cells are located in the brain.
Towards this, they implanted electrodes directly into the hippocampus and the surrounding region of a rat that was allowed to run around freely in a large box. The signals from the electrodes were analyzed using a computer, as the rat ran around the box, thus generating a map of its movements. Next, they chemically inactivated (numbed) chosen regions of the hippocampus and the surrounding region, a thin strip of a tissue called the entorhinal cortex (ERC) and watched. To their surprise, they found that the message to fire place cells in the hippocampus actually flowed from cells in the ERC.
Studying these ERC cells and their signals as a rat goes to a specific spot in the box, they found that the signals on the computer screen were not simple but arranged in a grid-like arrangement’— a hexagonal pattern much like a honeycomb!
As Dr Alison Abbot points out in her lucid summary of the work in the 9 October 2014 issue of the journal Nature, there are no physical hexagons traced on the floor of the box; these shapes are abstractly created in the rat’s brain and imposed on the environment — the code in the brain language, using which the rat navigates space and locations.
Even more striking is the arrangement of the grid-generating cells (called the grid cells) in the ERC. AS we move from the top part of the ERC strip to the bottom, the pattern expands from narrow spacing to bigger grids in steps or modules. And they expand by a constant factor (of 1.4) in each step of the module!
The mathematical features of the hexagonal patterns and the definite modules have attracted theoreticians. Dr Alison Abbot quotes the computational neuroscientist Dr. Andreas Herz of Munich, Germany who exclaims: “It (these findings) was so unexpected that the brain would use the same simple geometric forms that we have been describing in mathematics for millennia.” It suggests also that babies, humans and rats, are born with a very primitive sense of where they are in space and that this sense develops as the brain adapts to the world. The poet talked about the “mind’s eye”. See how prescient this phrase has been.
Finally, the work also highlights how important working with animals as models is. The recent banning of animal experiments in schools and colleges has been a bad move, and needs to be rescinded.

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