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Schizophrenia linked to loss of cells in brain’s memory centre for the first time.

Scientists have long speculated that schizophrenia, which affects about 1 in every 100 adults worldwide, originates in part in the hippocampus, the brain’s headquarters for memory and spatial navigation. As a result, nearly every region of the hippocampus has been studied extensively in the hopes of gaining insight into the disorder. However, one notable exception is a tiny region of the hippocampus known as CA2.  Now, a study from researchers at Columbia University and the Université Paris Descartes has shown that deficits in social memory may be due to a decrease in the number of a particular class of brain cells, namely inhibitory neurons, within the CA2 region of the brain’s memory centre.  The team state that their findings explain some of the underlying mechanisms that lead to the more difficult-to-treat symptoms of schizophrenia, such as social withdrawal, reduced motivation and decreased emotional capacity.  The opensource study is published in the journal Neuron.

Previous studies show that the smaller and less well-defined part of the hippocampus, the CA2 was like a small island that was depicted on old maps and remained unexplored.  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 behaviours, 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.  The current study shows mice display impaired social cognition, providing a potential mechanism and a neural substrate for this impairment in psychiatric disorders.

The current study examined the brains of these mice to show 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. Results show that the modified mice had a significantly reduced capacity for social memory compared with the controls.

Data findings show several age-dependent CA2 alterations, namely a decrease in the density of parvalbumin-expressing interneurons, a reduction in the amount of feedforward inhibition, and a change in CA2 pyramidal-neuron intrinsic properties. Furthermore, the group observe that area CA2 is less plastic in the neurogenetic schizophrenic mouse-model, making it nearly impossible to evoke action potential firing in CA2 pyramidal neurons.  Results show that the specific alterations reported in hippocampal CA2 in humans with schizophrenia are also present in these mice and may underlie impaired social cognition in this disorder.

The lab state that this raises the hypothesis that changes to CA2 may account for some of the social behavioural changes that occur in individuals with the disorder.  They go on to add that even the timing of the emergence of symptoms in the mice, during young adulthood, parallels the onset of schizophrenia in humans.

The team surmise that the global medical community can now examine the effects of schizophrenia at the cellular level and at the behavioural level.  For the future, researchers state that this essentially opens up a whole new avenue for research that could lead to earlier diagnosis and more effective treatments for schizophrenia.

Source: Columbia University’s Mortimer B. Zuckerman Mind Brain Behavior Institute

 

This is a mouse hippocampus with the CA2 region stained light blue. In the researchers' mouse model of schizophrenia, this region showed significant depletion of CA2 inhibitory neurons (shown here as white/magenta spots) and was accompanied by a deficit in social memory. Credit: Vivien Chevaleyre.
This is a mouse hippocampus with the CA2 region stained light blue. In the researchers’ mouse model of schizophrenia, this region showed significant depletion of CA2 inhibitory neurons (shown here as white/magenta spots) and was accompanied by a deficit in social memory. Credit: Vivien Chevaleyre.

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