Publication Date:
2014-04-04
Description:
The formation of precise connections between retina and lateral geniculate nucleus (LGN) involves the activity-dependent elimination of some synapses, with strengthening and retention of others. Here we show that the major histocompatibility complex (MHC) class I molecule H2-D(b) is necessary and sufficient for synapse elimination in the retinogeniculate system. In mice lacking both H2-K(b) and H2-D(b) (K(b)D(b)(-/-)), despite intact retinal activity and basal synaptic transmission, the developmentally regulated decrease in functional convergence of retinal ganglion cell synaptic inputs to LGN neurons fails and eye-specific layers do not form. Neuronal expression of just H2-D(b) in K(b)D(b)(-/-) mice rescues both synapse elimination and eye-specific segregation despite a compromised immune system. When patterns of stimulation mimicking endogenous retinal waves are used to probe synaptic learning rules at retinogeniculate synapses, long-term potentiation (LTP) is intact but long-term depression (LTD) is impaired in K(b)D(b)(-/-) mice. This change is due to an increase in Ca(2+)-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Restoring H2-D(b) to K(b)D(b)(-/-) neurons renders AMPA receptors Ca(2+) impermeable and rescues LTD. These observations reveal an MHC-class-I-mediated link between developmental synapse pruning and balanced synaptic learning rules enabling both LTD and LTP, and demonstrate a direct requirement for H2-D(b) in functional and structural synapse pruning in CNS neurons.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016165/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016165/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Hanmi -- Brott, Barbara K -- Kirkby, Lowry A -- Adelson, Jaimie D -- Cheng, Sarah -- Feller, Marla B -- Datwani, Akash -- Shatz, Carla J -- EY02858/EY/NEI NIH HHS/ -- R01 EY002858/EY/NEI NIH HHS/ -- R01 EY013528/EY/NEI NIH HHS/ -- R01 EY13528/EY/NEI NIH HHS/ -- R01 MH071666/MH/NIMH NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- England -- Nature. 2014 May 8;509(7499):195-200. doi: 10.1038/nature13154. Epub 2014 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Biology and Neurobiology and Bio-X, James H. Clark Center, 318 Campus Drive, Stanford, California 94305, USA. ; Department of Molecular and Cell Biology & Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA. ; 1] Departments of Biology and Neurobiology and Bio-X, James H. Clark Center, 318 Campus Drive, Stanford, California 94305, USA [2] Sage Bionetworks, 1100 Fairview Avenue N., Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695230" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/metabolism
;
Geniculate Bodies/*cytology/*physiology
;
H-2 Antigens/genetics/immunology/metabolism
;
Histocompatibility Antigen H-2D/genetics/immunology/*metabolism
;
Long-Term Potentiation/physiology
;
Long-Term Synaptic Depression
;
Mice
;
*Neural Pathways
;
Receptors, N-Methyl-D-Aspartate/metabolism
;
Retina/*cytology/*physiology
;
Retinal Ganglion Cells/cytology/physiology
;
Synapses/*metabolism
;
Synaptic Transmission
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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