The flow of copper in the brain has a previously unrecognized role in learning, memory and cell death, School of Medicine researchers have found.
The researchers’ findings suggest that copper and its transporter, a protein called Atp7a, are vital to human thinking. They speculate that variations in the genes coding for Atp7a, as well as other proteins of copper homeostasis, could partially account for differences in thinking among individuals.
Using rat and mouse nerve cells to study the role of copper in the brain, the team found that the Atp7a protein shuttles copper to neural synapses, the junctions that allow nerves to converse.
At synapses, the metal ions affect important components responsible for making neural connections stronger or weaker. The changing strength of neural connections — called synaptic plasticity — accounts for our ability to remember and learn, among other things.
“Why don’t we think a hundred times better than we do?” asked senior author Jonathan D. Gitlin, M.D., the Helene B. Roberson Professor of Pediatrics. “One answer to that question is, perhaps we could — if the brain could make the right connections. We’ve found that copper modulates very critical events within the central nervous system that influence how well we think.”
Neuroscience graduate students Michelle Schlief, Ph.D., and Tim West, Ph.D., led the research in collaboration with Anne Marie Craig, Ph.D., and David M. Holtzman, M.D., the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology. It appears online in the Proceedings of the National Academy of Sciences.
They found that when a chemical signal, or neurotransmitter, hits one of the microscopic antennas present at nerve synapses, Atp7a reacts and quickly brings copper ions from their storage areas within nerve cells to the cell surface.
When released into neural synapses, the copper damps down the activity of these antennas, called NMDA receptors. The activity of NMDA receptors determines how strong the connections between nerves cells are and changes in the receptors’ activity are critical to cell survival, learning and memory.
“The plasticity of the connections between neurons is important for nerve cell survival and for our ability to think the way we do,” said Gitlin, director of genetics and genomic medicine at St. Louis Children’s Hospital and scientific director of the Children’s Discovery Institute. “The NMDA receptors are a large component of this process, and we’ve found that Atp7a and copper are key factors controlling them.”