GABAERGIC STIMULATION REGULATES THE PHENOTYPE OF HIPPOCAMPAL INTERNEURONS THROUGH THE REGULATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR

gamma-Aminobutyric acid (GABA) switches from enhancing to repressing b rain-derived neurotrophic factor (BDNF) mRNA synthesis during the matu ration of hippocampal neurons in vitro. Interneurons do not produce BD NF themselves, but BDNF enhances their differentiation. Therefore, the question arose whether hippocampal interneurons regulate their phenot ype by regulating BDNF expression and release from adjacent cells. The GABA(A) receptor agonist muscimol and BDNF increased the size and neu ropeptide Y (NPY) immunoreactivity of hippocampal interneurons. Howeve r, GABAergic stimulation failed to increase NPY immunoreactivity in cu ltures from BDNF knockout embryos. At later developmental stages, when GABA represses BDNF synthesis, treatment with muscimol induced a decr ease in cell size and NPY immunoreactivity of interneurons. Interneuro ns might thus control their phenotype through the regulation of BDNF s ynthesis in, and release from, their target neurons.