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Neuron. 2015 Aug 19;87(4):781-96. doi: 10.1016/j.neuron.2015.07.020.

Neuroligins Sculpt Cerebellar Purkinje-Cell Circuits by Differential Control of Distinct Classes of Synapses.

Author information

1
Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, 265 Campus Drive, Room G1021, Stanford, CA 94305, USA.
2
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
3
Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, 265 Campus Drive, Room G1021, Stanford, CA 94305, USA. Electronic address: tcs1@stanford.edu.

Abstract

Neuroligins are postsynaptic cell-adhesion molecules that bind presynaptic neurexins and are genetically linked to autism. Neuroligins are proposed to organize synaptogenesis and/or synaptic transmission, but no systematic analysis of neuroligins in a defined circuit is available. Here, we show that conditional deletion of all neuroligins in cerebellar Purkinje cells caused loss of distal climbing-fiber synapses and weakened climbing-fiber but not parallel-fiber synapses, consistent with alternative use of neuroligins and cerebellins as neurexin ligands for the excitatory climbing-fiber versus parallel-fiber synapses. Moreover, deletion of neuroligins increased the size of inhibitory basket/stellate-cell synapses but simultaneously severely impaired their function. Multiple neuroligin isoforms differentially contributed to climbing-fiber and basket/stellate-cell synapse functions, such that inhibitory synapse-specific neuroligin-2 was unexpectedly essential for maintaining normal climbing-fiber synapse numbers. Using systematic analyses of all neuroligins in a defined neural circuit, our data thus show that neuroligins differentially contribute to various Purkinje-cell synapses in the cerebellum in vivo.

PMID:
26291161
PMCID:
PMC4545494
DOI:
10.1016/j.neuron.2015.07.020
[Indexed for MEDLINE]
Free PMC Article

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