title: E-cadherin is required at GABAergic synapses in cultured cortical neurons.
abstract: Classical cadherins are cell adhesion molecules that are thought to contribute to the control of synapse formation, synaptic transmission, and synaptic plasticity. This is largely based on studies investigating the functions of N-cadherin at glutamatergic synapses, whereas other classical cadherins have hardly been examined at central synapses. We have now used a conditional knockout approach in cultured cortical neurons to address the role of E-cadherin mainly at inhibitory, GABAergic synapses. Cortical neurons were cultured from mouse fetuses carrying floxed E-cadherin alleles in homozygous configuration. E-cadherin knockout was induced in individual neurons by expression of an EGFP-Cre fusion protein. Immunocytochemical stainings for the vesicular GABA (VGAT) and glutamate (VGLUT1) transporters revealed a reduced density of dendritic GABAergic synapses in E-cadherin knockout neurons, whereas glutamatergic synapses were unaffected. Electrophysiological recordings of miniature and action potential-evoked, GABA(A) receptor-mediated postsynaptic currents confirmed an impairment of GABAergic synapses at the functional level. In summary, our immunocytochemical and electrophysiological analysis of E-cadherin knockout neurons suggested that E-cadherin signaling importantly contributes to the regulation of GABAergic synapses in cortical neurons.
authors.affiliation: Institute for Neuro- and Sensory Physiology, Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fiederling
authors.forename: Roman
authors.initials: R
authors.lastname: Ewert
authors.forename: Aksana
authors.initials: A
authors.lastname: Andreyeva
authors.forename: Kay
authors.initials: K
authors.lastname: Jüngling
authors.forename: Kurt
authors.initials: K
authors.lastname: Gottmann
mesh_terms: D000818:Animals; D015820:Cadherins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development* / Q000502:physiology; D059330:GABAergic Neurons / Q000166:cytology / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D061251:Primary Cell Culture; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D015820:Cadherins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid