RESUMO
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).
Assuntos
Encéfalo/fisiologia , Complexo CD3/fisiologia , Antígenos de Histocompatibilidade Classe I/fisiologia , Plasticidade Neuronal , Neurônios/fisiologia , Sinapses/fisiologia , Animais , Encéfalo/crescimento & desenvolvimento , Complexo CD3/genética , Potenciais Pós-Sinápticos Excitadores , Perfilação da Expressão Gênica , Genes MHC Classe I , Corpos Geniculados/fisiologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Antígenos de Histocompatibilidade Classe I/genética , Hibridização In Situ , Potenciação de Longa Duração , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Mutantes , Vias Neurais , Receptores de GABA-A/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Retina/crescimento & desenvolvimento , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Transdução de Sinais , Transmissão Sináptica , Vias VisuaisRESUMO
When contacts are first forming in the developing nervous system, many neurons generate spontaneous activity that has been hypothesized to shape appropriately patterned connections. In Mustela putorius furo, monocular intraocular blockade of spontaneous retinal waves of action potentials by cholinergic agents altered the subsequent eye-specific lamination pattern of the lateral geniculate nucleus (LGN). The projection from the active retina was greatly expanded into territory normally belonging to the other eye, and the projection from the inactive retina was substantially reduced. Thus, interocular competition driven by endogenous retinal activity determines the pattern of eye-specific connections from retina to LGN, demonstrating that spontaneous activity can produce highly stereotyped patterns of connections before the onset of visual experience.
