Now, three laboratories at the University of Pennsylvania have come together using electrophysiological, anatomical, and immunohistochemical approaches to understand how schizophrenia works at the cellular level, especially in identifying how the changes in the interaction between different types of nerve cells leads to symptoms of the disease.
"Our work provides a model linking genetic risk factors for schizophrenia to a functional disruption in how the brain responds to sound, by identifying reduced activity in special nerve cells that are designed to make other cells in the brain work together at a very fast pace.
"We know that in schizophrenia this ability is reduced, and now, knowing more about why this happens may help explain how loss of a protein called dysbindin leads to some symptoms of schizophrenia," lead scientist Gregory Carlson said.
Previous genetic studies had found that some forms of the gene for dysbindin were found in people with schizophrenia.
Most importantly, a prior finding at Penn showed the dysbindin protein is reduced in a majority of schizophrenia patients, suggesting it is involved in a common cause of the disease.
For the current research, the scientists used a mouse with a mutated dysbindin gene to understand how reduced dysbindin protein may cause symptoms of schizophrenia.
The team demonstrated a number of sound-processing deficits in the brains of mice with the mutated gene. They discovered how a specific set of nerve cells that control fast brain activity lose their effectiveness when dysbindin protein levels are reduced.
These specific nerve cells inhibit activity, but do so in an extremely fast pace, essentially turning large numbers of cells on and off very quickly in a way that is necessary to normally process the large amount of information travelling into and around the brain, according to the findings published in the 'Proceedings of the National Academy of Sciences'.
