Island cells and the formation of episodic memory

 News Editor: Tina Pentland

The ability to correctly associate temporal information in episodic memory is an essential tool for survival.  For example, animals must be able to control the fear response, based on information in memory, in order to respond appropriately to a predator or other threat, being neither too careless nor too fearful; similarly, the human brain needs to know when to act against a potential threat, and when the danger can be ignored.

Neuroscientists at MIT, led by Dr Susumu Tonegawa, Picower Professor of Biology and Neuroscience, and Director of the RIKEN Brain Science Institute, have now discovered how two neural circuits in the cerebral cortex, between the entorhinal cortex and the hippocampus, regulate the formation of time-linked memories in the brain.  These findings are described in the paper “Island Cells Control Temporal Association Memory” published last week in the journal Science.  As Dr Tonegawa notes, it is important to be able to form temporal associations in memory, but at the same time to have the ability (like animals) to filter information and “to know what events [to] associate, and what not to associate”.

Episodic memories are formed by the hippocampus communicating with an adjacent region in the cerebral cortex, known as the entorhinal cortex, which is made up of several layers that receive and process sensory information.  These memories are based on three essential elements—what, where, and when—that must be properly integrated for memories to form.  They provide information about the object or event itself (what), the place or context (where), and the time sequence (when).  While knowledge about how the brain processes information linking the object and the place (the object-place mechanism) is quite well advanced, until now the third link in the chain that provides the essential information to enable formation of temporal associations (the object-time mechanism) has not been well understood.

The research described in this paper builds on an earlier study from 2011 that identified the necessary brain circuit (called the monosynaptic circuit), between layer 3 of the entorhinal cortex and the hippocampus, that allowed mice to link memories of two events—a sound followed by an electric shock—with an interval of up to 20 seconds.  Perhaps most exciting was the discovery that when this circuit was disrupted, the mice showed no fear of the tone—they failed to associate the two events in memory.

In this new study, the researchers report the discovery of a previously unknown circuit originating from neurons that form circular clusters in layer 2 of the entorhinal cortex, dubbed “island cells”, which suppresses the monsynaptic circuit.  Then, using a technique called optogenetics, which allows specific neurons to be switched on or off with light, the researchers investigated how temporal associations were affected by manipulating the interactions of the two circuits.  They found, in particular, that island cells can set a threshold on remembering, thus providing the necessary discrimatory ability to control whether or not a memory will form. “We are the first to identify a circuit that negatively affects memory formation”, Dr Tonegawa said.


Takashi Kitamura, Michele Pignatelli, Junghyup Suh, Keigo Kohara, Atsushi Yoshiki, Kuniya Abe, and Susumu Tonegawa. Island Cells Control Temporal Association Memory. Science, 23 January 2014 DOI: 10.1126/science.1244634

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