Tweaking developing synapses

This study by Carla Shatz and colleagues offers a fascinating insight into the non-immune functions of MHC class I molecules. MHC class I molecules (and other immunological mediators) have been implicated in synapse elimination in the central nervous system (CNS). However, it has been unclear if these molecules regulate developing synapses, and whether a neuronal or immune function is involved. The authors found that the mouse MHC class I molecule H2-D^b is essential for synapse elimination during the development of the visual system. Mice that lacked both H2-D^b and H2-K^b showed defects in synapse elimination and in the formation of eye-specific layers in visual processing areas of the brain, but this could be rescued by restoring H2-D^b expression exclusively in CNS neurons. Polymorphisms in the MHC locus have been linked to schizophrenia, and the authors propose that differential MHC class I expression during brain development could affect synaptic pruning and lead to long-lasting changes in human brain circuits and behaviour.