Long-term memory in the cortex

Memories (red) for associating two different sensations are formed in the cortex (tone in blue and touch in yellow).

“WHERE” and “how” memories are encoded in a nervous system is one of the most challenging questions in biological research. Mazahir T. Hasan (Max Planck Institute (MPI) for Medical Research, Heidelberg) and Jose Maria Delgado-Garcìa (University Pablo de Olavide of Seville, Spain) have provided the first experimental evidence that a specific form of memory associations is encoded in the cerebral cortex and is not localised in the hippocampus as most neuroscience textbooks would say. The new study is a game changer since, according to it, the motor cortical circuits themselves, and not the hippocampus, are used for memory storage.

The researchers investigated the learning behaviour of genetically modified mice in which NMDA receptors were turned off only in the motor cerebral cortex. NMDA receptors are the central molecular elements involved in increasing or decreasing transmission of the signals to synapses, and hence form an important element in the learning process. The new study shows that in the motor cortex this so-called synaptic plasticity no longer functions without the NMDA receptors. On the basis of the new findings, it is the cerebral cortex, not the hippocampus, that is the storage site for some forms of memory. This was verified through behaviour tests on animals with and without NMDA receptors in the primary motor cortex. They had to learn to link a tone with a subsequent electrical stimulus of the eyelid. This association of two sensory inputs involves the cerebellum, which coordinates the necessary movements, and the hippocampus and the cerebral cortex, which are important learning and memory centres.

The work has complemented the findings of other Heidelberg researchers that the hippocampus is not the seat of memory. In July 2012, Rolf Sprengel and Peter Seeburg from the MPI discovered that mice without NMDA receptors in the hippocampus were still capable of learning. An advanced and detailed knowledge of the mechanisms for the acquisition, consolidation, and recall of associations in the brain is the prerequisite for a therapeutic treatment of the devastating effects of memory loss in various neurological conditions, such as amnesia and Alzheimer’s disease.