Distinct α GABAAR subunits influence structural and transcriptional properties of CA1 hippocampal neurons

The hippocampus is recognized as a major telencephalic area modulating learning and episodic memory through the activation of its different subregions. The various functional properties of Ammon's horn 1 (Cornu Amonis 1; CA1) area have been shown to rely on GABAergic and Glutamat- (Glu)-ergic neuronal signals during both postnatal and adult stages. For this purpose, it was the aim of the present study to establish whether certain alpha GABAAR subunits (alpha2,5) were capable of modifying CA1 structural and functional features via their interaction with specific NMDA receptor subunits such as NR1 during early development stages of the hibernating hamster (Mesocricetus auratus). Indeed, in vitro addition of the selective alpha2,5 GABAAR agonist diazepam (DZP; alpha2,5) accounted for early neuronal formations that were blocked by its antagonist flumazenil (FLM). In particular, the former drug caused very great (p < 0.001) increases of dendritic sprouting and branching processes mainly at day in vitro (DIV) 3, while its effects still continued to be responsible for moderate (p < 0.05) increases of axonal length during the entire culture period. Contextually, DZP was also responsible for a very great up-regulated expression of neuritic NR1 and MAP2 together with a great (p < 0.01) increase of synaptophysin at DIV7. Overall, this first study suggests a specifically tight cross-talking relationship of GABAergic/Gluergic mechanisms operating during CA1 neuronal development, which may bring us closer to the identification of more selective therapeutic targets for hippocampal-linked neurological disorders.

► GABAergic effects on hamster CA1 hippocampal neuronal morphology at PND5.
► α2,5-Containing GABAARs differentially regulate neuritic sprouting and branching.
► α2,5 subunits interfere with expression of Syp, MAP2 and NR1 throughout development.
► CA1 neuronal morpho-functional responses may have clinical implications.