From The Cover: A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy
Abstract
Recently, MHC class I molecules have been shown to be important for the retraction of synaptic connections that normally occurs during development [Huh, G.S., Boulanger, L. M., Du, H., Riquelme, P. A., Brotz, T. M. & Shatz, C. J. (2000) Science 290, 2155-2158<pub-id pub-id-type="pmid">11118151</pub-id>]. In the adult CNS, a classical response of neurons to axon lesion is the detachment of synapses from the cell body and dendrites. We have investigated whether MHC I molecules are involved also in this type of synaptic detachment by studying the synaptic input to sciatic motoneurons at 1 week after peripheral nerve transection in β2-microglobulin or transporter associated with antigen processing 1-null mutant mice, in which cell surface MHC I expression is impaired. Surprisingly, lesioned motoneurons in mutant mice showed more extensive synaptic detachments than those in wild-type animals. This surplus removal of synapses was entirely directed toward inhibitory synapses assembled in clusters. In parallel, a significantly smaller population of motoneurons reinnervated the distal stump of the transected sciatic nerve in mutants. MHC I molecules, which traditionally have been linked with immunological mechanisms, are thus crucial for a selective maintenance of synapses during the synaptic removal process in neurons after lesion, and the lack of MHC I expression may impede the ability of neurons to regenerate axons.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- December 2004
- DOI:
- 10.1073/pnas.0408154101
- Bibcode:
- 2004PNAS..10117843O
- Keywords:
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- NEUROSCIENCE