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Distinct circuit-dependent functions of presynaptic neurexin-3 at GABAergic and glutamatergic synapses.


ABSTRACT: ?- and ?-neurexins are presynaptic cell-adhesion molecules whose general importance for synaptic transmission is well documented. The specific functions of neurexins, however, remain largely unknown because no conditional neurexin knockouts are available and targeting all ?- and ?-neurexins produced by a particular gene is challenging. Using newly generated constitutive and conditional knockout mice that target all neurexin-3? and neurexin-3? isoforms, we found that neurexin-3 was differentially required for distinct synaptic functions in different brain regions. Specifically, we found that, in cultured neurons and acute slices of the hippocampus, extracellular sequences of presynaptic neurexin-3 mediated trans-synaptic regulation of postsynaptic AMPA receptors. In cultured neurons and acute slices of the olfactory bulb, however, intracellular sequences of presynaptic neurexin-3 were selectively required for GABA release. Thus, our data indicate that neurexin-3 performs distinct essential pre- or postsynaptic functions in different brain regions by distinct mechanisms.

SUBMITTER: Aoto J 

PROVIDER: S-EPMC4482778 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Distinct circuit-dependent functions of presynaptic neurexin-3 at GABAergic and glutamatergic synapses.

Aoto Jason J   Földy Csaba C   Ilcus Silviana Maria Ciurea SM   Tabuchi Katsuhiko K   Südhof Thomas C TC  

Nature neuroscience 20150601 7


α- and β-neurexins are presynaptic cell-adhesion molecules whose general importance for synaptic transmission is well documented. The specific functions of neurexins, however, remain largely unknown because no conditional neurexin knockouts are available and targeting all α- and β-neurexins produced by a particular gene is challenging. Using newly generated constitutive and conditional knockout mice that target all neurexin-3α and neurexin-3β isoforms, we found that neurexin-3 was differentially  ...[more]

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