Synapse elimination and learning rules coregulated by MHC Class I H2-Db
| Autor: | Akash Datwani, Carla J. Shatz, Marla B. Feller, Barbara K. Brott, Lowry A. Kirkby, Hanmi Lee, Sarah Cheng, Jaimie D. Adelson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Retinal Ganglion Cells
General Science & Technology 1.1 Normal biological development and functioning Long-Term Potentiation Biology Receptors N-Methyl-D-Aspartate Synaptic Transmission Article Retina Synapse 03 medical and health sciences Mice 0302 clinical medicine Underpinning research Receptors Neural Pathways Animals Long-term depression Histocompatibility Antigen H-2D Eye Disease and Disorders of Vision 030304 developmental biology 0303 health sciences Multidisciplinary Synaptic pharmacology Long-Term Synaptic Depression Neurosciences H-2 Antigens Geniculate Bodies Long-term potentiation Retinal waves Cell biology Synaptic fatigue nervous system Silent synapse Immunology Neurological Synapses Calcium Synaptic tagging 030217 neurology & neurosurgery N-Methyl-D-Aspartate |
| Zdroj: | Nature Nature, vol 509, iss 7499 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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 (α-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. |
| Databáze: | OpenAIRE |
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