Better understanding of the region of the hippocampus, called CA2, could prove useful in understanding and treating disorders characterized by altered social behaviours, such as autism, schizophrenia, and bipolar disorder, said researchers at Columbia University Medical Center (CUMC).

Scientists have long understood that the hippocampus plays a critical role in our ability to remember who, what, where and when of our daily lives.

Recent studies have shown that different sub-regions of the hippocampus have different functions. The dentate gyrus is critical for distinguishing between similar environments, while CA3 enables us to recall a memory from partial cues. The CA1 region is critical for all forms of memory.

"However, the role of CA2, a relatively small region of the hippocampus sandwiched between CA3 and CA1, has remained largely unknown," said senior author Steven A Siegelbaum, professor of neuroscience and pharmacology, chair of the Department of Neuroscience.

To learn more about this part of the hippocampus, the researchers created a transgenic mouse in which CA2 neurons could be selectively inhibited in adult animals.
Once the neurons were inhibited, the mice were given a series of behavioural tests.

"The mice looked quite normal until we looked at social memory," said first author Frederick L Hitti, who developed the transgenic mouse.
"Normally, mice are naturally curious about a mouse they've never met; they spend more time investigating an unfamiliar mouse than a familiar one. In our experiment, however, mice with an inactivated CA2 region showed no preference for a novel mouse versus a previously encountered mouse, indicating a lack of social memory," Hitti said.
In two separate novel-object recognition tests, the CA2-deficient mice showed a normal preference for an object they had not previously encountered, showing that the mice did not have a global lack of interest in novelty.

In another experiment, the researchers tested whether the animals' inability to form social memories might have to do with deficits in olfaction (sense of smell), which is crucial for normal social interaction. However, the mice showed no loss in ability to discriminate social or non-social odours.

"Because several neuropsychiatric disorders are associated with altered social behaviours, our findings raise the possibility that CA2 dysfunction may contribute to these behavioural changes," said Siegelbaum.

This possibility is supported by findings of a decreased number of CA2 inhibitory neurons in individuals with schizophrenia and bipolar disorder and altered vasopressin signaling in autism. Thus, CA2 may provide a new target for therapeutic approaches to the treatment of social disorders.


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