Chronic application brain-derived neurotrophic factor strengthens GABAergic synaptic transmission

Abstract

To elucidate chronic actions of brain-derived neurotrophic factor (BDNF) on GABAergic synapses, we examined effects of a long-term application (for 10-15 days) of BDNF on synaptic activity of solitary GABAergic neurons cultured on glial microislands. Evoked and miniature inhibitory postsynaptic currents (IPSCs) were recorded in the whole-cell voltage-clamp mode. The application of BDNF at 100 ng/ml enhanced the amplitude of evoked IPSCs and increased the frequency of miniature IPSCs. Such actions of BDNF were blocked by anti-TrkB antibody. In contrast, BDNF did not have a detectable effect on the amplitude of miniature IPSCs and the paired pulse ratio of IPSCs evoked by paired shocks. To evaluate morphological changes, neurons were immunocytochemically stained with anti- microtubule-associated protein 2 antibodies, to visualize somatodendritic region and anti-synapsin I antibodies, to visualize presynaptic sites. A quantitative morphological analysis indicated that BDNF increased the number of dendritic branches and synaptic sites. To visualize functionally active presynaptic sites, neurons were stained with a styryl dye, FM1-43. BDNF increased the number of FM1-43-positive sites that was correlated with the frequency of miniature IPSCs. These results suggest that the chronic treatment with BDNF strengthens GABAergic synaptic transmission. [Jpn J Physiol 54 Suppl:S143 (2004)]