Researchers have created what they see as the first animal model of schizophrenia by reducing the inhibition of nerve cells involved in reasoning and complex decision.
Dr. Lin Mei Medical College of Georgia and his colleagues developed in mice, a model of impaired balance between excitation and inhibition of these cells which may occur in schizophrenia. Their work is published in the Proceedings of the National Academy of Sciences.
The mice appear to have changed and certain behaviors of people with Alzheimer’s disease. The researchers believe that this model will help identify better treatments. They are testing the effectiveness of antipsychotic drugs (neuroleptics) currently on the market.
The researchers created the mice by deleting, in interneurons, a gene potentially associated with schizophrenia, the ErbB4. Interneurons are the nerve cells (or neurons) that help in exerting an inhibitory slow neurons (called pyramidal cells) of the prefrontal cortex-related decisions.
In previous work, the research team had identified how the gene ErbB4 and another gene, neuregulin-1, worked together to balance the activity of these pyramidal cells. They reported in 2007 in the journal Neuron that these two genes contribute to maintaining a healthy balance between excitation and inhibition by increasing the release of GABA, an inhibitory neurotransmitter important for communication between cells in the prefrontal cortex.
The ErbB4 gene deletion alters the balance between excitation and inhibition in preventing the contribution of the inhibitory GABA to pyramidal cells. This had the effect of lead in mice, potentially similar behavior to behavior characteristic of schizophrenia, including impaired memory in the short term.
Dr. Mei is assumed that in people with schizophrenia, the prefrontal cortex interneurons do not play their normal role of inhibition of pyramidal cells and that the core level excitation of the latter is probably high.