title: Endogenous BDNF regulates inhibitory synaptic transmission in the ventromedial nucleus of the hypothalamus.
abstract: Output from steroidogenic factor-1 (SF-1) neurons in the ventromedial nucleus of the hypothalamus (VMH) is anorexigenic. SF-1 neurons express brain-derived neurotrophic factor (BDNF) that contributes to the regulation of food intake and body weight. Here I show that regulation of GABAergic inputs onto SF-1 neurons by endogenous BDNF determines the anorexigenic outcome from the VMH. Single-cell RT-PCR analysis reveals that one-third of SF-1 neurons express BDNF and that only a subset of BDNF-expressing SF-1 neurons coexpresses the melanocortin receptor type 4. Whole cell patch-clamp analysis of SF-1 neurons in the VMH shows that exogenous BDNF significantly increases the frequency of spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs). This enhancement of GABA drive readily decreases the excitability of SF-1 neurons. However, treatment with BDNF has no significant effect on the frequency of TTX-independent GABAergic IPSCs. Moreover, TrkB receptors are not localized at the postsynaptic sites of GABAergic synapses on SF-1 neurons as there is no change in the amplitude of miniature IPSCs in the presence of BDNF. Dual patch-clamp recordings in mouse hypothalamic slices reveal that stimulation of one SF-1 neuron induces an increase in sIPSC frequency onto the neighboring SF-1 neuron. More importantly, this effect is blocked by a tyrosine kinase inhibitor. Hence, this increased GABA drive onto SF-1 neurons may, in part, explain the cellular mechanisms that mediate the anorexigenic effects of BDNF.
authors: Albert Einstein College of Medicine, Dept. of Medicine, Division of Endocrinology, 1300 Morris Park Ave., Bronx, NY 10461, USA. young-hwan.jo@stonybrook.edu
authors: Young-Hwan
authors: YH
authors: Jo
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000503:physiopathology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor