The 2014 Nobel Prizein

Medicine

Bui Dac Chi,MD

Medic Center

In his will, Alfred Nobel stipulated that one part of his fortune should be awarded "the person who shall have made the most important discovery within the domain of physiology or medicine".

Q u e s t i o n s a b o u t p l a c e a n d n a v i g a t i o n h a v e e n g a g e d p h i l o s o p h e r s a n d s c i e n t i s t s f o r a l o n g t i m e . M o r e t h a n 2 0 0 y e a r s a g o , t h e G e r m a n p h i l o s o p h e r I m m a n u e l K a n t a r g u e d t h a t s o m e m e n t a l a b i l i t i e s e x i s t a s a p r i o r i k n o w l e d g e , i n d e p e n d e n t o f e x p e r i e n c e . H e c o n s i d e r e d t h e c o n c e p t o f s p a c e a s a n i n b u i l t p r i n c i p l e o f t h e m i n d , o n e t h r o u g h w h i c h t h e w o r l d i s a n d m u s t b e p e r c e i v e d . W i t h t h e a d v e n t o f b e h a v i o u r a l p s y c h o l o g y i n t h e m i d ‐ 2 0 t h c e n t u r y, t h e s e q u e s t i o n s c o u l d b e a d d r e s s e d e x p e r i m e n t a l l y. W h e n E d w a r d To l m a n e x a m i n e d r a t s m o v i n g t h r o u g h l a b y r i n t h s , h e f o u n d t h a t t h e y c o u l d l e a r n h o w t o n a v i g a t e , a n d p r o p o s e d t h a t a “ c o g n i t i v e m a p ” f o r m e d i n t h e b r a i n a l l o w e d t h e m t o f i n d t h e i r w a y. B u t q u e s t i o n s s t i l l l i n g e r e d ‐ h o w w o u l d s u c h a m a p b e r e p r e s e n t e d i n t h e b r a i n ?

• He found that a certain type of nerve cell was always activated when a rat was at a certain place in a room. Other nerve cells were activated when the rat moved to another place. He demonstrated that these "place cells" were building up a map, not just registering visual input

The Mosers further explored the relationship between grid cells and place cells in theoretical models, lesion experiments, and in remapping experiments . These and other studies by Mosers and O’Keefe, as well as by others, have shown that there is a reciprocal influence between grid cells in the medial entorhinal cortex and place cells in the hippocampus and that other spatially-tuned cells in the entorhinal cortex, in particular the border cells , may contribute in the generation of the firing pattern of the place cell.

“The Hippocampus as a Cognitive Map” “The Hippocampus as a Cognitive Map”

The grid and place cell systems are found in many mammalian species including humans

It is an emergent theme that place-coding cells in the hippocampal structures are involved in storing and/or retrieving spatial memories. In the 1950s Scoville and Milner (1957) published their report on the patient Henry Molaison (HM), who had his two hippocampi surgically removed for treatment of epilepsy. The loss of hippocampi caused severe memory deficits, as evident by the clinical observation that HM was unable to encode new memories, while he could still retrieve old memories. HM had lost what has later been named episodic memory, referring to our ability to remember self-experienced events. There is no direct evidence that place cells are coding episodic memory. However, place cells can encode not only for the current spatial location, but also where the animal has just been and where it is going next. The past and present may also be overlapping in time in place cells when animals are rapidly tele-transported between two physical different environments.

After a memory has been encoded, the memory undergoes further consolidation, e.g. during sleep. Ensemble recording with multi-electrodes in sleeping animals has made possible the study of how memories of spatial routes achieved during active navigation are consolidated. Groups of place cells that are activated in a particular sequence during the behaviour display the same sequence of activation in episodes during the subsequent sleep.

Together the activity of place cells may be used both to define the position in the environment at any given time, and also to remember past experiences of the environment. Maybe related to this notion is the findings that the hippocampus of London taxi drivers, which undergoes extensive training to learn how to navigate between thousands of places in the city without a map, grew during the year long training period and that the taxi drivers after this training had significantly larger hippocampal volume than control subjects.

There is no effective way to prevent or cure most of the brain disorders. The episodic memory is affected in several brain disorders, including dementia and Alzheimer’s disease. A better understanding of neural mechanisms underlying spatial memory is therefore important, and the discoveries of place and grid cells have been a major leap forward to advance this endeavour. The knowledge about the brain’s navigational system might help understand the cognitive decline seen in patients with Alzheimer’s disease.

The 2014 Nobel Prize in Physiology or Medicine is awarded to Dr. John M. O’Keefe, Dr. May-Britt Moser and Dr. Edvard I. Moser for their discoveries of nerve cells in the brain that enable a sense of place and navigation. These discoveries are ground breaking and provide insights into how mental functions are represented in the brain and how the brain can compute complex cognitive functions and behaviour. An internal map of the environment and a sense of place are needed for recognizing and remembering our environment and for navigation. This navigational ability, which requires integration of multi-modal sensory information, movement execution and memory capacities, is one of the most complex of brain functions.

• The work of the 2014 Laureates has radically altered our understanding of these functions. John O’Keefe discovered place cells in the hippocampus that signal position and provide the brain with spatial memory capacity. May-Britt Moser and Edvard I. Moser discovered in the medial entorhinal cortex, a region of the brain next to hippocampus, grid cells that provide the brain with an internal coordinate system essential for navigation. Together, the hippocampal place cells and the entorhinal grid cells form interconnected nerve cell networks that are critical for the computation of spatial maps and navigational tasks. The work by John O’Keefe, May-Britt Moser and Edvard Moser has dramatically changed our understanding of how fundamental cognitive functions are performed by neural circuits in the brain and shed new light onto how spatial memory might be created.

Why are these cells so important? A major aim of neuroscience is to provide a description for how our thoughts and behaviour arise from individual cells. This is not so hard for sensation and action, but when it comes to recalling the past or planning a route through space it’s a huge challenge, and that’s where place cells and grid cells come in. They provide a tangible link between the activity of a single cell and complex “higher-level” behaviour.