Asian Scientist (Jan. 28, 2014) – Researchers have discovered a new cell type in the brains of mice that inhibits the ability to connect two events separated in time into a single experience.
The study, published in the journal Science, report the discovery of a novel brain circuit that may be responsible for limiting our brain’s capacity for temporal association.
Temporal association is a property of memory that links two events that happen seconds or minutes apart into one experience. For example, hearing a car horn can prompt a pedestrian to glance around to check if there is any danger from oncoming traffic.
The memory association of a car horn warning of an approaching car is formed by the intercommunication of two brain areas called the entorhinal cortex and the hippocampus. This link is known to depend on a part of the entorhinal cortex called the MECIII (medial entorhinal cortex layer III), which sends projections to neurons in a region of the hippocampus called CA1.
In this study, researchers identified a new cell type in layer II of the entorhinal cortex that also send their bundle projections to the CA1 region of the hippocampus. However, unlike the MECIII neurons, these newly-identified “Island” cells connect to a cell type that suppresses the memory-making neurons in CA1.
The Island cells form clusters surrounded by Ocean cells that make up the majority of cells in this layer. Ocean cells are known to send projections to another part of the hippocampus called the dentate gyrus, which processes the context of a memory, such as the location where the event took place.
“It was surprising to discover that Island cells project to the hippocampus,” said study first co-author Dr. Takashi Kitamura, “because the circuit diagram between the entorhinal cortex and the hippocampus was considered complete.”
To determine the role of Island cells in setting temporal association during memory formation, Dr. Kitamura and colleagues manipulated Island cells in the brains of mice and observed their behavior.
Mice were trained to link two events — a tone and a mild electric shock — that occur up to 20 seconds apart. Initially, mice did not fear the tone, but after three trials, they showed a fear response to the tone—freezing in place—indicating that they feared the shock.
To see how temporal association was affected when Island cells were manipulated, the researchers used a recent technique called optogenetics that allows specific neurons to be switched on or off with light.
When Island cell activity was increased mice could not associate the tone with the shock and did not freeze upon hearing the tone. Conversely, when Island cells were shut off mice froze for a longer time after the tone and could be trained with a milder shock.
The researchers concluded that Island cells suppress the formation of temporal associations and their activity sets a threshold for whether a memory will form. This ability may allow the brain to remember events based on their relative importance and disregard events that are trivial.
For example, a failure to remember that a car horn predicts an oncoming car could be dangerous. In the opposite case, forming associations when none exist could make an individual anxious and expecting imaginary danger.
“In memory research, there was no evidence for this type of circuit,” said Dr. Kitamura. “We are the first to identify a circuit that negatively affects memory formation.”
Future work will explore the role of the circuit in other memories.
The article can be found at: Kitamura T et al. (2014) Island Cells Control Temporal Association Memory.
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Source: RIKEN.
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