Neuroscientists at the Massachusetts Institute of Technology believe they have discovered two neural circuits that coordinate how time-linked memories are formed and stored in the brain.

Scientists already know that memories of events (called “episodic memories”) are created in the hippocampus area of the brain. The hippocampus receives information from the entorhinal cortex (a region of the central cortex), which processes sensory information.

Research on animals has told us that neurons in the brain, called “place cells,” fire when an animal is in a specific location that is linked to a memory.

This explains how the brain can link memories and locations, but experts know relatively little about how objects and time are associated in the brain.

The researchers behind the new study, published in the journal Science, found some answers to this in a 2011 study they conducted on mice. By linking memories of two separate sensory experiences – a sound and an electric shock, occurring 20 seconds apart – and analyzing the mice’s neural responses, they located the circuit connecting the hippocampus to the entorhinal cortex in the mouse brains.

By disrupting this circuit (called the “monosynaptic circuit”), the scientists were able to prevent the mice from associating the sound with the shock – they no longer feared the sound.

Island Cells Make Clusters in Entorhinal Cortex Layer IIShare on Pinterest
Cells making clusters in the entorhinal cortex layer II – green shows Island cells, while red shows Ocean cells.
Image credit: RIKEN

In the new study, the researchers built on their 2011 work by discovering a second – previously unknown – circuit that can suppress the monosynaptic circuit. The researchers discovered in this circuit a new type of neuron, which they called “island cells,” because of their clustered, circular formation.

Previously, the mice that the Massachusetts Institute of Technology (MIT) team had studied were unable to link the memories of the sound and the shock for more than 20 seconds. However, in the new study, the scientists found they were able to both manipulate this recall period and make it longer or shorter.

They found that boosting the activity of cells in the third layer of the entorhinal cortex would allow the mice to make the memory connection over longer periods of time. To shorten this recall period, the researchers could reduce activity of the third layer cells, or they could stimulate the newly discovered island cells, which had the same effect.

Both of the methods used to shorten the link of the sound and shock resulted in “turning down” the activity in the hippocampus. So, from this, the researchers deduce that it is prolonged activity in a specific area of the hippocampus (called “CA1”) that keeps these two memories linked.

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Green shows axons of Island cells, while blue shows the nuclei. Red shows the marker of CA2 region.
Image credit: RIKEN

The researchers believe that it is the balance of these two neural circuits – the monosynaptic circuit and the island cells – that allow us to respond to signs of approaching danger, without being over-sensitive to sensory information, or “paralyzed with fear.”

“It’s important for us to be able to associate things that happen with some temporal gap,” says study author Prof. Susumu Tonegawa, who is a member of MIT’s Picower Institute for Learning and Memory. “For animals it is very useful to know what events they should associate, and what not to associate.”

Recently, Medical News Today reported on another study examining memory association between sound and electric shock in mice subjects. The researchers behind that study – from the Medical College of Georgia at Georgia Regents University – found they could break the memory connection in the mice by disrupting a receptor in the hippocampus called the N-methyl-D-aspartate receptor.