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 modifications. Here, we show that in mice genetically deficient for cell surface class I MHC or for a class I MHC receptor component, CD3zeta, refinement of connections between retina and central targets during development is incomplete. In the hippocampus of adult mutants, N-methyl-D-aspartate receptor-dependent long-term potentiation (LTP) is enhanced, and long-term depression (LTD) is absent. Specific class I MHC messenger RNAs are expressed by distinct mosaics of neurons, reflecting a potential for diverse neuronal functions. These results demonstrate an important role for these molecules in the activity-dependent remodeling and plasticity of connections in the developing and mature mammalian central nervous system (CNS).
Huh
G S
GS
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. gshuh@alum.mit.edu
Boulanger
L M
LM
Du
H
H
Riquelme
P A
PA
Brotz
T M
TM
Shatz
C J
CJ
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000502:physiology*; D017252:CD3 Complex / Q000235:genetics / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D020869:Gene Expression Profiling; D005805:Genes, MHC Class I; D005829:Geniculate Bodies / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D017774:Long-Term Potentiation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009434:Neural Pathways; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012160:Retina / Q000254:growth & development / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000502:physiology; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D014795:Visual Pathways
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D015395:Histocompatibility Antigens Class I; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate