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None of us has satnav in our brains, so how do we navigate through three-dimensional space? The hippocampus has proven to assist this process by reminding us of movements we have previously made to achieve a certain goal. The NMDA receptor is an important link in this process.


These are the findings of researchers at the University of Amsterdam (UvA), whose research results have been published in the scientific journal Neuron

Imagine you are in a labyrinth and trying to find the exit. First you turn left, then right, until you finally find the exit. You then enter again and need to find the right way a second time from the same starting point. What strategy do you use? You could decide to follow the same left-right sequence of movements you made the first time. You could also try to navigate according to 'landmarks' in the environment, such as a tree protruding out above the labyrinth which seemed close to the exit the first time. In the first instance, you rely on your memory of a sequence of movements you have already made; the second approach relies on the spatial orientation of objects in the environment.

Missing NMDA receptor

UvA researcher Henrique Cabral and fellow researchers from the Swammerdam Institute for Life Sciences examined the electrical activity of neurons in the hippocampi of mice trying to find their way out of such a maze. Their goal was to find out whether this activity was disrupted in mice that were missing a certain protein molecule in their hippocampus, one that is known to serve an important memory function in that area of the brain. The missing molecular link is the NMDA receptor, which enables the links between brain cells to be altered in the long term.

The mice were sent through the maze twice. Like humans, they too could locate the goal the second time either by making a series of movements, or by following landmarks in the environment. Mice missing the NMDA receptor had no problem navigating according to the landmarks. However, their ability to recreate a complex sequence of left and right turns was affected significantly.

This defect was also clearly evident in the electrical activity of the cells in the hippocampus, which have the special property of becoming electrically active ('firing' impulses) whenever the animal is at a specific place in an environment. This location varies from cell to cell. In mice that followed the landmarks, the cells exhibited a normal pattern of impulses that corresponded to the coding of the locations in the maze where the mouse had already been. Yet the location coding among mice relying on their memory of a sequence of movements became muddled in those missing the NDMA receptor, whereas it was normal among the mice that still had the receptor.

These research results shed a surprising new light on the way in which brains map out spatial routes. It was previously thought that the hippocampus was mainly important for visual, object-oriented navigation, whereas it has now been shown that this also applies to sequences of movements.  

The study was funded by a grant from Technology Foundation STW.

Publication details

H. Cabral, M.A. Vinck, C. Fouquet, C.M.A. Pennartz, L. Rondi-Reig and F.P. Battaglia. Oscillatory dynamics and place field maps reflect sequence and place memory processing in hippocampal ensembles under NMDA receptor control. Neuron (22 January 2014).