How Immune Cells Help Wire the Brain: Implications for Autism and Psychiatric Illness

In this lecture, Dr. Beth Stevens will discuss recent work that implicates brain immune cells, called microglia, in sculpting of synaptic connections during development and their relevance to autism, schizophrenia and other brain disorders.

Recent research has revealed a key role for microglia and a group of immune-related molecules, called complement, in normal developmental synaptic pruning, a process required to establish precise brain wiring. Emerging evidence from Stevens’ lab and others suggest aberrant regulation of this pruning pathway may contribute to synaptic and cognitive dysfunction in a host of brain disorders, including schizophrenia. Studies also suggest that a person’s risk of schizophrenia is increased if he or she inherits specific variants in complement C4, which plays a well-known role in the immune system but also helps sculpt developing synapses in the mouse visual system.

Together these findings may help explain known features of schizophrenia, including reduced numbers of synapses in key cortical regions and an adolescent age of onset that corresponds with developmentally timed waves of synaptic pruning in these regions. Stevens will discuss this and ongoing work to understand the mechanisms by which complement and microglia prune specific synapses in the brain. A deeper understanding of how these immune mechanisms mediate synaptic pruning may provide novel insight into how to protect synapses in autism and other brain disorders.