Endogenous BDNF regulates inhibitory synaptic transmission in the ventromedial nucleus of the hypothalamus

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12 Scopus citations

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 neu-rotrophic 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 melanocor-tin 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 GABAe-rgic IPSCs. Moreover, TrkB receptors are not localized at the post-synaptic 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.

Original languageEnglish (US)
Pages (from-to)42-49
Number of pages8
JournalJournal of neurophysiology
Volume107
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • GABA
  • Neural circuitry
  • Obesity
  • Presynaptic receptor
  • TrkB receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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