Abstract
Synaptogenesis, the generation and maturation of functional synapses between nerve cells, is an essential step in the development of neuronal networks in the brain. It is thought to be triggered by members of the neuroligin family of postsynaptic cell adhesion proteins, which may form transsynaptic contacts with presynaptic alpha- and beta-neurexins and have been implicated in the etiology of autism. We show that deletion mutant mice lacking neuroligin expression die shortly after birth due to respiratory failure. This respiratory failure is a consequence of reduced GABAergic/glycinergic and glutamatergic synaptic transmission and network activity in brainstem centers that control respiration. However, the density of synaptic contacts is not altered in neuroligin-deficient brains and cultured neurons. Our data show that neuroligins are required for proper synapse maturation and brain function, but not for the initial formation of synaptic contacts.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Vesicular Transport
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Animals
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Animals, Newborn
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Blotting, Western
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Brain / cytology
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Brain / metabolism
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Brain / physiology*
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Brain Stem / metabolism
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Brain Stem / physiology
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Cell Adhesion Molecules, Neuronal
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Cells, Cultured
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Gene Expression / genetics
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In Situ Hybridization
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Membrane Proteins / physiology*
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Mice
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Mice, Knockout
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Microscopy, Electron
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology*
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Neurons / cytology
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Neurons / metabolism
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Neurons / ultrastructure
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Phenotype
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Respiratory Insufficiency / genetics
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Respiratory Insufficiency / physiopathology
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Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / metabolism
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Synapses / genetics
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Synapses / physiology*
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Synapses / ultrastructure
Substances
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Adaptor Proteins, Vesicular Transport
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Cell Adhesion Molecules, Neuronal
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Membrane Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
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complexin II
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neuroligin 1
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neuroligin 2
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neuroligin 3