Functional requirement for class I MHC in CNS development and plasticity

Class I major histocompatibility complex (class I MHC) molecules, known to be important for immune responses to antigen, are expressed also by neurons that undergo activity-dependent, Long-term structural and synaptic modific ations. Here, we show that in mice genetically deficient for cell surface c lass I MHC or for a class I MHC receptor component, CD3 zeta, refinement of connections between retina and central targets during development is incom plete. In the hippocampus of adult mutants, N-methyl-D-aspartate receptor-d ependent Long-term potentiation (LTP) is enhanced, and Long-term depression (LTD) is absent. Specific class I MHC messenger RNAs are expressed by dist inct mosaics of neurons, reflecting a potential for diverse neuronal functi ons. These results demonstrate an important role for these molecules in the activity-dependent remodeling and plasticity of connections in the develop ing and mature mammalian central nervous system (CNS).