Ina Köhler, Lisa-Marie Rennau, Leon Hoffmann, Ekaterina Demianchuk, Michelle Kaczmarski, Eric Sobierajski, Christian Riedel, Petra Wahle
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引用次数: 0
Abstract
GluN2D-containing NMDA receptors are expressed in early postnatal interneurons, but their role is enigmatic. We tested whether treatment with the GluN2C/D positive allosteric modulator CIQ and non-competitive antagonist DQP-1105 from days in vitro (DIV) 5-10 and DIV 15-20 modulates neurite growth in organotypic cultures. Calcium imaging confirmed a functional expression of GluN2D in nonpyramidal neurons. DQP treatment enhanced apical dendritic branching and increased ERK1/2 phosphorylation and spine density, suggesting a disinhibitory effect mirrored by a reduced expression of GAD-65, VGAT, and Syt-2. Control basket cells had larger axon-carrying dendrites (AcDs), and under CIQ, the AcDs grew even larger. The axons of CIQ-treated basket cells formed more branches within the dendritic field, and the effect was strongest for axons emerging from AcDs. DQP-treated basket cells also displayed more complex AcDs, presumably driven by enhanced network activity. However, local branching of basket cell axons was reduced under DQP in somatic axon cells but at control level in AcD cells. This suggested a growth-promoting effect of the enhanced network activity and that the AcD configuration neutralized the inhibitory action of DQP on basket cell axons. The results suggest a specific role of GluN2D signaling for development and remodeling of interneuronal axons.
期刊介绍:
Cerebral Cortex publishes papers on the development, organization, plasticity, and function of the cerebral cortex, including the hippocampus. Studies with clear relevance to the cerebral cortex, such as the thalamocortical relationship or cortico-subcortical interactions, are also included.
The journal is multidisciplinary and covers the large variety of modern neurobiological and neuropsychological techniques, including anatomy, biochemistry, molecular neurobiology, electrophysiology, behavior, artificial intelligence, and theoretical modeling. In addition to research articles, special features such as brief reviews, book reviews, and commentaries are included.