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CSHL links activity in brain synapses and developmental abnormalities with schizophrenia gene

May 25, 2007

The neuregulin-1 receptor ErbB4 controls glutamatergic synapse maturation and plasticity

Cold Spring Harbor, NY " Cold Spring Harbor Laboratory (CSHL) researchers have identified a function of neuregulin1 (NRG1), a gene previously linked to schizophrenia but whose role in the disease was unknown. "We found that when this gene or this pathway is impaired," explained CSHL's Bo Li. "It starts a chain reaction negatively impacting synapses in the brain which contribute to the abnormal development of brain circuits and may lead to schizophrenia."

By discovering the connections between genes and how they impact synapses and circuits in the brain, research is guiding the development of new strategies to diagnose and treat neurological disease. Published on May 24, 2007 in the journal Neuron, this latest research supports the hypothesis that schizophrenia is a disease that results from multiple factors, including genetic defects and developmental abnormalities in the brain. A lynchpin in the development of the disease is the brain's neurotransmitter system known as the glutamate system. When the glutamate system is suppressed it leads to abnormal brain development and schizophrenic symptoms.

Unlocking the mystery of NRG1 and its critical function in the normal development of the glutamate system was the result of a unique combination of technologies at CSHL. Under the direction of CSHL's Neuroscience Research Program Chair, Robert Malinow, M.D., Ph.D., researchers inform their study of diseased brains by the ongoing study of normal brains. "The ability to finally identify the functionality of NRG1 was possible here because of access to powerful technology that combined the ability to manipulate individual genes, to study the very structure of the glutamate synapse with a two-photon microscope, and to perform functional studies using electrophysiology."

Li hopes that his research will stimulate more exploration of the functions of NRG1 in the brain. "This gene and its pathway also have implications for other neurological diseases such as bipolar disorder. Knowing the cellular and molecular mechanisms of NRG1, we can now more intensely study the impact on complex brain circuits that define the aberrant behavior of these diseases," said Li.

Cold Spring Harbor Laboratory