The brainchild is now four years old. Since the Centre for the Biology of Memory (CBM) was inaugurated in December 2002, it has provided some of the most important insights so far into how spatial location and spatial memory are computed in the brain.

While the first years at the CBM were used to test and expand hypotheses outlined in the original research plan, the agenda was soon overtaken by the exciting discovery of grid cells in the entorhinal cortex. As we prepare for the second half of the Centre’s lifetime, the ultimate goals remain unaltered, but priorities have changed and a number of new questions and techniques have emerged. It is becoming clear that a deeper understanding of the workings of cortical microcircuits requires a cross-disciplinary experimental-theoretical approach using some of the latest tools for selective intervention with specific elements of the neuronal circuits.

The discovery of grid cells is the result of a 10-year-long research programme aimed at determining how the brain computes location and how information about location is stored in memory. The hippocampus consists of several serially organised subfields with different inputs and outputs. The structural differences between the subfields laid the foundation for hypotheses about how each subfield contributes to spatial representation. In several papers published between 2004 and 2007, Jill and Stefan Leutgeb showed, together with colleagues, that certain cell assemblies in the CA3 area of the hippocampus perform pattern completion and pattern separation, and that pattern separation is supported by processes that enhance differences between input signals. These processes are located upstream at the entrance of the hippocampus, in the dentate gyrus.

While our insights into internal hippocampal computational processes were considerably enhanced by these studies, other experiments drew our attention to the cortical input and output regions of the hippocampus. The first important step in this direction was taken when Vegard Brun and colleagues showed in 2002 that direct inputs from the entorhinal cortex are sufficient for place representation in the CA1 cells of the hippocampus. His observations led Marianne Fyhn and others to record electrical activity directly from the entorhinal cortex, and in 2004 she reported that the entorhinal cortex contains an accurate, topographically arranged spatial map of the animal’s environment.

In 2005, Torkel Hafting and colleagues, recording from the same area, discovered the grid cell – a cell type different from any other functional cell category in the nervous system. These cells fire electrical signals with remarkable periodicity and this, together with the representation of direction and distance in the same network, as discovered by Sargolini and colleagues in 2006, pointed to a possible role for the entorhinal cortex in the computation of self-location based on movement.

Finally, at the beginning of 2007, Marianne Fyhn and others found that coordinate changes in grid cells predict pattern separation processes downstream in the hippocampus, which linked the entorhinal studies directly to the previously published studies of hippocampal computational functions.

This body of work has resulted in eight original papers, which were published in Nature and Science from 2002 to 2007. The grid-cell data, characterised by Science as the most important discovery in the field for more than two decades (Science, 5 May 2006), have brought us closer to understanding how the brain computes where we are and how we get from one place to another.

I would like to use this opportunity to thank every member of the Centre – visiting professors, post-docs, graduate students, master’s students and technical and administrative staff – for their important contributions to these achievements. Likewise, I am grateful to the Board of CBM, the Advisory Board, the Institute of Neuromedicine, the Faculty of Medicine and the rectorship of NTNU for their enthusiastic support.

Where will we be going during the next five years? While we will continue pursuing the original aim of understanding the computational functions of hippocampal networks, and the interaction between the hippocampus and the rest of the cortex, we will use the grid cells as an experimental model for understanding computation in neuronal circuits in general. Spatial representation is beginning to be one of the best understood non-sensory brain functions, and studies of mechanisms by which neuronal circuits keep track of an animal’s location are likely to uncover computational mechanisms applied by neuronal networks across the entire cortex. The structural symmetry of the grid cells is unique in that it is generated by the nervous system rather than derived from sensory input. Understanding its origins thus offers a direct window into some of the most fundamental operational principles of neuronal assemblies and microcircuits. To understand neuronal computation at the network level, we will use a combination of modelling and experimental testing. One of the most important developments will be the introduction of new technologies for cell-type-specific gene silencing, which in my view could provide us with a unique opportunity for determining the functions of the many diverse cell classes in the network.