Neuroligin-4: Einfluss auf die synaptische Übertragung exzitatorischer Neurone der Schicht IV des Barrel-Kortex

Abstract

Neuroligins (NL) are predominant postsynaptically localized transmembrane adhesion molecules that interact with the presynaptically localized protein neurexin. There are different NL-isoproteins (NL 1 – NL 4) that differ in their association to excitatory and inhibitory synapses. Neuroligins play an important role in maturation and function of synapses. Their functional and clinical relevance is demonstrated by the association between mutations of the NL isoprotein NL-4 and neuropsychiatric diseases like autism spectrum disorders. Immunohistochemical experiments have shown that NL-4 is localized in the retina where it plays a role in inhibitory synaptic transmission. However no link between the immunohistochemical localization of NL-4 in layer IV of the barrel-cortex and inhibitory synapses was observed. These findings and the predominant excitatory synaptic connections by thalamocortical projections and column-associated neocortical circuitries in layer IV leads to the question of whether NL-4 interacts with excitatory synapses in this area. To address this question this work observed the excitatory synaptic transmission to excitatory neurons in layer IV of barrel-cortex. Therefore AMPA-receptor mediated excitatory postsynaptic currents (EPSC) of layer IV spiny stellate cells, star pyramidal and pyramidal cells were recorded using the patch-clamp technique. The analysis of the recorded EPSC showed significant differences in the EPSC-kinetics between NL-4-WT and NL-4-KO neurons. The decay time of EPSC in NL-4-KO neurons was significantly longer, the maximum decay slope and maximum rise slope significantly lower than in NL 4-WT neurons. These findings suggest a functional relevance of NL-4 for the AMPA-receptor mediated synaptic transmission to excitatory neurons in Layer IV of barrel-cortex. The pattern of alterations indicates a change in biophysical AMPA-receptor characteristics in NL-4 neurons that might be caused by alterations of synaptically expressed AMPA-receptor/TARP subunits which are related to NL via postsynaptic scaffolding proteins of the postsynaptic density (like PSD-95 and S SCAM).