Brain-derived neurotrophic factor promotes gephyrin protein expression and GABAA receptor clustering in immature cultured hippocampal cells

• In immature neuronal cultures, long-term incubation with BDNF increased the protein expression and clustering of gephyrin.
• BDNF treatment promoted the interaction of GABAAR with gephyrin.
• GABAAR clustering at synaptic sites increased after long-term incubation with BDNF.

Fast synaptic inhibition in the adult brain is largely mediated by GABAA receptors (GABAAR). GABAAR are anchored to synaptic sites by gephyrin, a scaffolding protein that appears to be assembled as a hexagonal lattice beneath the plasma membrane. Brain derived neurotrophic factor (BDNF) alters the clustering and synaptic distribution of GABAAR but mechanisms behind this regulation are just starting to emerge. The current study was aimed to examine if BDNF alters the protein levels and/or clustering of gephyrin and to investigate whether the modulation of gephyrin is accompanied by changes in the distribution and/or clustering of GABAAR. Exogenous application of BDNF to immature neuronal cultures from rat hippocampus increased the protein levels and clustering of gephyrin. BDNF also augmented the association of gephyrin with GABAAR and promoted the formation of GABAAR clusters. Together, these observations indicate that BDNF might regulate the assembly of GABAergic synapses by promoting the association of GABAAR with gephyrin.