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Brain Remapping Dysfunction Causes Spatial Memory Impairment in Alzheimer’s Disease

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Alzheimer’s disease is one of the most serious diseases in an aging society, yet the cause is often unclear and there is no appropriate treatment method. Many patients with Alzheimer’s disease develop spatial memory impairment which causes symptoms such as wandering, putting a great stress on caregivers. However, the cause of spatial memory impairment has been long unclear.

A research group led by Kei Igarashi, an assistant professor at University of California, Irvine elucidated the brain circuit mechanism that cause of spatial memory impairment in Alzheimer’s disease. The research group used Alzheimer’s disease model mice developed at RIKEN in 2014 and analyzed the brain activity of mice performing memory behaviors using an electrophysiological technique. The results showed that brain function to distinguish different locations called as “remapping”, a function of the hippocampus of healthy brain, become impaired. The results also showed that this hippocampal dysfunction was caused by decreased activity in the brain region called the entorhinal cortex.

These results indicate that the impairment of remapping causes spatial memory impairment in Alzheimer’s disease. In the future, improving brain remapping function may reverse spatial memory impairment in patients with Alzheimer’s disease, for example using deep brain stimulation methods.

The study was conducted jointly with Takaomi Saido, a team leader at the RIKEN and Professor Takashi Saito at Nagoya City University, as part of the JST Strategic Basic Research Programs.

(1)Electrophysiological technique

This is a method for directly measuring electrical signals using metal electrodes for recording brain activity.


The function of place cells and grid cells to distinguish different rooms. Since there are countless place cells in the hippocampus, every time an animal moves into a different room, activity patterns of many place cells will change all at once. Since the combination of place cell group patterns is different in each room, combinations of place cells create spatial memory of different locations.


The memory center of the brain. The hippocampus, the Greek word for seahorse, is so named because it has a shape similar to that of a seahorse. It has special electric circuits to store and recall memory information. When the hippocampus is damaged, memory impairment occurs.

(4)Entorhinal cortex

A part of the brain that forms the memory center of the brain along with the hippocampus. Information from various parts of the brain enters the hippocampus through the entorhinal cortex and is stored in memory. The information stored in the hippocampus is transferred to various parts of the brain through the entorhinal cortex. Therefore, damage to the entorhinal cortex also causes memory impairment.


HeechulJun, AllenBramian, ShogoSoma, TakashiSaito, Takaomi C.Saido and Kei M.Igarashi, “Disrupted Place Cell Remapping and Impaired Grid Cells in a Knockin Model of Alzheimer's Disease”, Neuron. Published online July 21, 2020, DOI: 10.1016/j.neuron.2020.06.023

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