A team of Stanford researchers has discovered that a molecule previously thought to exclusively play a role in the immune system is in fact both necessary and sufficient for pruning connections between neurons in the visual system, in a breakthrough that opens the door to further advances in the field.
According to Hanmi Lee, a research associate in the lab of Professor of Biology Carla Shatz and the study’s first author, babies are born with an enormous number of connections in their brains. Those connections are strengthened over time as neurons fire in sync, though the further refinement of vision requires that some unnecessary neuronal connections be cut back.
“You need the proper activity pattern and proper experiences…to get rid of the wrong connections and strengthen the right ones,” said Jaimie Adelson Ph.D. ’14, who collaborated on the study.
In previous years, Shatz’s lab had published work that found that a group of proteins — major histocompatibility complex (MHC) — which play a major part in the immune system also had a role in the development of the nervous system.
Mice genetically engineered to lack two particular MHC proteins (namely D and K) not only had poorly functional immune systems, but also visual systems; unrelated parts of the two eyes had formed and strengthened connections, and the mice were unable to tell basic shapes apart. Until the publication of this study, however, it was unclear whether the immune system was responsible for the nervous system’s pruning.
Adelson and Barbara Brott, a research assistant in the Shatz lab and collaborator on this study, noted that the genetic engineering necessary to address this question could be very challenging. Lee, however, said that she had “found a shortcut.”
A group of mice she engineered only expressed D and K in their brains; while their immune systems were still heavily compromised, their visual system worked normally. The out-of-sync visual system neurons had been disconnected, even if the immune system was barely functioning.
The research team found that in the absence of D, receptors on the surface of neurons that are usually impermeable to calcium in newborns had high permeability to the ion. These receptors consist of a different proportion of their usual subunits, which influences their permeability to calcium. While synapse strengthening is only slightly increased in the absence of D, no synapse weakening and elimination occurs.
The exact mechanism through which D affects the composition of those receptors remains unknown, however. The research team said that they next hope to understand how D, and potentially K, regulate the composition of the receptors.
The group also plans to extend their investigation to other parts of the brain, such as the cortex, while part of the Shatz lab is already working on understanding developmental disorders arising from problems with neural plasticity.
“It’s time to understand when there are abnormal expression levels of protein D—nobody is working on this now,” Lee said.
Contact Silviana Ilcus at smci ‘at’ stanford ‘dot’ edu.