Researchers have found that deficits in social memory--a crucial yet poorly understood feature of psychiatric disorders such as schizophrenia--may be due to a decrease in the number of a particular class of brain cells, called inhibitory neurons, in a little-explored region within the brain's memory center.

The findings, which were reported in the journal Neuron, explain some of the underlying mechanisms that lead to the more difficult-to-treat symptoms of schizophrenia, including social withdrawal, reduced motivation and decreased emotional capacity.

Several discoveries have focused attention on a possible association between CA2 and schizophrenia. This region of the hippocampus is associated with vasopressin, a hormone that plays a role in sexual bonding, motivation and other intensely social behaviors, which become impaired in people with the disorder. In addition, postmortem examinations of people with schizophrenia have revealed a marked decrease in the number of CA2 inhibitory neurons, while the rest of the hippocampus remained largely unaffected. However, the significance of this loss had remained unclear.

In this study, the researchers performed a series of electrophysiological and behavioral experiments on a mouse model of schizophrenia developed.
By examining the brains of these mice, the researchers observed a substantial decrease in inhibitory CA2 neurons, as compared to a control group of normal, healthy mice--a change remarkably similar to that previously observed in postmortem examinations of people with schizophrenia.

Moreover, the team discovered that the modified mice had a significantly reduced capacity for social memory compared with the controls. This raises the hypothesis that changes to CA2 may account for some of the social behavioral changes that occur in individuals with the disorder.

"Even the timing of the emergence of symptoms in the mice--during young adulthood--parallels the onset of schizophrenia in humans," said Joseph Gogos, lead author.

"We can now examine the effects of schizophrenia at the cellular level and at the behavioral level," said Steven Siegelbaum, PhD, chair of the Department of Neuroscience at CUMC, a principal investigator at the Zuckerman Institute and a co-author of the paper. "This essentially opens up a whole new avenue for research that could lead to earlier diagnosis and more effective treatments for schizophrenia."

http://zuckermaninstitute.columbia.edu/news/loss-cells-brains-memory-center-linked-schizophrenia