"Inner GPS", a far-reaching influence in brain research-For the Nobel Prize in Physiology or Medicine 2014.

Abstract

On the day of Oct. 6, 2014, John O’Keefe and a Norwegian couple May-Britt Moser and Edvard Moser won the Nobel Prize in Physiology or Medicine for discovering the “inner GPS” that functions in the brain when the animals navigate through the world. The prize was awarded for their work in identifying the cells that make up the positioning system in the mammalian brain. Hippocampal “place cells” are presumably the principal cells in each of the layers that fire in complex bursts when an animal moves through a specific location. In 1971, by recording electrophysiological signals, O’Keefe discovered the “place cells” in the rat hippocampus and proposed that the hippocampus functions as a cognitive map for spatial memory [1]. He observed that place cells spike at different phases relative to theta rhythm oscillations in hippocampal local field potential. As a rat enters the firing field of a place cell, the spiking starts during late phases of the theta rhythm, and as the rat moves through the firing field, the spikes shift to earlier phases of the theta cycle (http://en.wikipedia.org/ wiki/John_O’Keefe_(neuroscientist)). This effect has been replicated in numerous other laboratories, providing evi-dence for the coding of sensory input by the timing of spikes. Thus, evidence from place cells offers strong sup-port for hippocampal involvement in spatial mapping [2]. Through the 1980s and 1990s, the prevailing theory was that the formation of place fields originated within the hip-pocampus itself (Scientific Background-Nobelprize.org). In 2002, May-Britt and Edvard Moser found that disconnect-ing projections from the entorhinal cortex through the CA3 did not abolish the CA1 place fields [3]. In a later study using larger arenas for the animals to move in, they discov-ered a novel neuronal cell type, the “grid cell,” with unusual properties [4]. The grid cell generates a coordinate system for precise positioning and pathfinding. The Mosers’ study demon-strated that grid cells in the rat entorhinal cortex help ani-mals to understand where they are [5]. They inserted elec-trodes into the rat entorhinal cortex and recorded electrical signals from individual grid cells as the rat ran around a box eating chocolate treats. A single grid cell fired when the rat crossed certain points on the floor; it turns out that these points formed a hexagonal grid, similar to a honeycomb. Results showed that each cell generates its own grid, and these overlapping patterns help the rat to recognize its loca-tion and direction. These discoveries have not only provided a better understanding of brain function in navigation, but have also opened novel avenues for studying cognitive functions (http://en.wikipedia.org/wiki/Grid_cell). The visual orientation columns are organized regions of neurons, which are excited by visual line stimuli of varying angles that are located in the primary visual cortex and span multiple cortical layers. The geometry of the orientation columns are arranged in slabs that are perpendicular to the surface of the primary visual cortex [6]. For visual orienta-tion, animals and humans create a typical ordinate with neurons in a quadrate (90) pattern (Figure 1A) in the pri-mary visual cortex, but a hexagonal (120) pattern with six triangles in the entorhinal cortex (Figure 1B). Does the