Type I TARPs promote dendritic growth of early postnatal neocortical pyramidal cells in organotypic cultures

Mohammad I.K. Hamad, Alexander Jack, Oliver Klatt, Markus Lorkowski, Tobias Strasdeit, Sabine Kott, Charlotte Sager, Michael Hollmann, Petra Wahle

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

The ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate receptors (AMPARs) have been implicated in the establishment of dendritic architecture. The transmembrane AMPA receptor regulatory proteins (TARPs) regulate AMPAR function and trafficking into synaptic membranes. In the current study, we employ type I and type II TARPs to modulate expression levels and function of endogenous AMPARs and investigate in organotypic cultures (OTCs) of rat occipital cortex whether this influences neuronal differentiation. Our results show that in early development [5-10 days in vitro (DIV)] only the type I TARP γ-8 promotes pyramidal cell dendritic growth by increasing spontaneous calcium amplitude and GluA2/3 expression in soma and dendrites. Later in development (10-15 DIV), the type I TARPs γ-2, γ-3 and γ-8 promote dendritic growth, whereas γ-4 reduced dendritic growth. The type II TARPs failed to alter dendritic morphology. The TARP-induced dendritic growth was restricted to the apical dendrites of pyramidal cells and it did not affect interneurons. Moreover, we studied the effects of short hairpin RNA-induced knockdown of endogenous γ-8 and showed a reduction of dendritic complexity and amplitudes of spontaneous calcium transients. In addition, the cytoplasmic tail (CT) of γ-8 was required for dendritic growth. Single-cell calcium imaging showed that the γ-8 CT domain increases amplitude but not frequency of calcium transients, suggesting a regulatory mechanism involving the γ-8 CT domain in the postsynaptic compartment. Indeed, the effect of γ-8 overexpression was reversed by APV, indicatingacontribution of NMDA receptors. Our results suggest that selected type I TARPs influence activity-dependent dendritogenesis of immature pyramidal neurons.

Original languageEnglish
Pages (from-to)1737-1748
Number of pages12
JournalDevelopment (Cambridge)
Volume141
Issue number8
DOIs
Publication statusPublished - Apr 2014
Externally publishedYes

Keywords

  • Dendritogenesis
  • Glutamate receptors
  • Interneurons
  • Neocortex
  • Postnatal development
  • TARPs

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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