Animal models of schizophrenia

A number of animal models have been developed to help explore the factors underlying schizophrenia in humans.

Calcineurin knockout mice
Mutations in the gene for calcineurin have been found in some people with schizophrenia. Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at MIT, and her team created laboratory mice lacking the gene for calcineurin in the forebrain and found that these mice displayed several behavioral symptoms of schizophrenia, including impaired short-term memory, attention deficits, and abnormal social behavior.

Subsequent work with these knockout mice found there was a disruption in the normal pattern of brain activity In normal mice, hippocampal place cells are assocatiated with specific aspects of a learnt path and fire in sequence when the mice stop using the path. This mental rehearsal continues when the mice are sleeping. These replays have been shown to reflect the presence of high frequency brain-wave oscillations known as ripple events. However in mice lacking calcineurin, during the intertrail period, their ripple events were much stronger and more frequent and the firing of the place cells was chaotic, suggesting that the mice were not replaying the route in the mormal way.

It has been suggested that, the role of calcineurin in normal mice is to suppress the connections in hippocampal neuronal synapses while in the mice knockout mice, long-term potentiation (LTP) is more prevalent and long-term depression (LTD), is suppressed.

It is possible that this abnormal hippocampual hyperactivity may reflect disruption of the default mode network and that this may play a role in information processing in the brains of people diagnoseeed with schizophrenia.