Published in Neuron, the study shows how Ocean cells encode surrounding contexts and are necessary for the formation of memories that make contextual learning possible.
Episodic memories—memories of events—are thought to be established in part though a neural circuit between two neighboring brain regions—the hippocampus and the entorhinal cortex. However, until now, no one had pinpointed where contexts are first represented in the brain. “Although many thought that the hippocampus generates context-specific information”, explains lead author Takashi Kitamura, “we found that this information is already formed in the entorhinal cortex before it reaches the hippocampus.”
The research team, led by Susumu Tonegawa, director of both the RIKEN Brain Science Institute in Japan and the RIKEN-MIT Center for Neural Circuit Genetics at MIT, first used live calcium imaging to visualize brain activity in active mice. High calcium levels indicate that neurons are working, and by placing markers in two types of entorhinal cells—Ocean cells and Island cells—the team could observe their responses to different contexts. After sequentially placing mice into two rooms that looked different, they found that while Island cells always showed the same amount of activity regardless of the room, many Ocean neurons were more active in either room 1 or room 2. This indicated that Ocean cells differentiate environmental contexts.
The team next investigated how entorhinal cells affected context-related neural activity in the hippocampus. After establishing that the activity of hippocampal neurons also discriminated between the two rooms, they found that this ability disappeared if Ocean cells were optogenetically inhibited with green light while the mice were in the rooms. In contrast, inhibiting Island cells had no effect. This shows that Ocean cells are responsible for identifying a context and then send this information to the hippocampus.
Contextual learning relies on our ability to make associations with and later recognize our surroundings. For example, one bad experience at the dentist can make simply sitting in a dentist’s office a very anxious experience later in life. This type of contextual learning is called fear conditioning, and is useful when studying learning and memory in animals. When the team inhibited Ocean cells in mice during fear conditioning, they found that the characteristic freezing response was greatly reduced when mice were later placed in the same room, meaning that the mice never associated the room’s context with the fearful experience.
“We have now discovered a role for Ocean cells in episodic memory that compliments that of Island cells,” says Kitamura. “Ocean cells contribute the contextual components of an experience, while Island cells contribute the temporal information. The next step is to understand how the two components are integrated in the brain to form memories”.
Contextual associations are a large part of episodic memory, and the entorhinal cortex is one of the first regions to be affected by Alzheimer’s disease. “We can already see neuronal loss in the entorhinal cortex during the early stages of Alzheimer’s disease,” says Kitamura. “Understanding how Ocean and Island cells contribute to specific types of memory formation may help to develop markers to improve early-phase diagnosis of AD.”
- Takashi Kitamura, Chen Sun, Jared Martin, Lacey J Kitch, Mark J Schnitzer and Susumu Tonegawa, “Entorhinal Cortical Ocean Cells Encode Specific Contexts and Drive Context-Specific Fear Memory”, Neuron, doi: 10.1016/j.neuron.2015.08.036
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