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Neuron. 2017 May 3;94(3):611-625.e4. doi: 10.1016/j.neuron.2017.04.011.

Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins.

Author information

1
Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, 265 Campus Drive, Stanford, CA 94305, USA.
2
Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, 265 Campus Drive, Stanford, CA 94305, USA. Electronic address: tcs1@stanford.edu.

Abstract

Neurexins are recognized as key organizers of synapses that are essential for normal brain function. However, it is unclear whether neurexins are fundamental building blocks of all synapses with similar overall functions or context-dependent specifiers of synapse properties. To address this question, we produced triple cKO (conditional knockout) mice that allow ablating all neurexin expression in mice. Using neuron-specific manipulations combined with immunocytochemistry, paired recordings, and two-photon Ca2+ imaging, we analyzed excitatory synapses formed by climbing fibers on Purkinje cells in cerebellum and inhibitory synapses formed by parvalbumin- or somatostatin-positive interneurons on pyramidal layer 5 neurons in the medial prefrontal cortex. After pan-neurexin deletions, we observed in these synapses severe but dramatically different synaptic phenotypes that ranged from major impairments in their distribution and function (climbing-fiber synapses) to large decreases in synapse numbers (parvalbumin-positive synapses) and severe alterations in action potential-induced presynaptic Ca2+ transients (somatostatin-positive synapses). Thus, neurexins function primarily as context-dependent specifiers of synapses.

KEYWORDS:

autism; cell-adhesion molecule; cerebellum; interneuron; neurexin; neuroligin; release probability; schizophrenia; synapse; synaptogenesis

PMID:
28472659
PMCID:
PMC5501922
DOI:
10.1016/j.neuron.2017.04.011
[Indexed for MEDLINE]
Free PMC Article

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