Stimulation of GABAergic neuron differentiation by NT-4/5 in cultures of rat cerebral cortex

Primary cultures of fetal rat cortical cells were used to investigate trophic effects of neurotrophin-4/5 (NT-4/5) on GABAergic neurons. Chronic administration of NT-4/5 resulted in a significant increase in high-affinity GABA uptake and in a stronger immunohistochemical staining pattern and bigger cells size of neurons visualized by GABA immunohistochemistry. Brain-derived neurotrophic factor (BDNF) exerted similar actions. These effects were observed in cultures prepared from rat fetuses from embryonic day (ED) 15 and ED18. The total number of cells was marginally increased in ED15 but not ED18 cultures. NT-4/5 did not elevate uptake of excitatory amino acids. Administration of NT-4/5 and BDNF resulted in higher levels of the calcium binding protein, calbindin, in these cultures. Our findings suggest that subpopulations of cortical GABAergic and calbindin-expressing neurons respond to NT-4/5 during development.