BDNF occludes GABA receptor-mediated inhibition of GABA release in rat hippocampal CA1 pyramidal neurons

Eur J Neurosci. 2006 Oct;24(8):2135-44. doi: 10.1111/j.1460-9568.2006.05092.x.

Abstract

During the development of the rat hippocampus, both gamma-aminobutyric acid (GABA)(B) autoreceptors and brain-derived neurotrophic factor (BDNF) play important roles in the formation of GABAergic synapses as well as in the GABA(A) receptor-mediated transmissions. While a number of studies have reported rapid effects of BDNF on GABA(A) receptor-mediated responses, the interactions between GABA(B) autoreceptors and BDNF are less clear. Using conventional whole-cell patch-clamp recordings, we demonstrated here that BDNF significantly occludes baclofen-induced suppression of GABA(A) receptor-mediated transmissions in each of the preparations including hippocampal slices prepared from P14 rats, hippocampal CA1 pyramidal neurons isolated from P14 and P21 rats, and cultured hippocampal pyramidal neurons. This effect of BDNF was rapid and reversible, and was mediated via the activation of presynaptic TrkB receptor tyrosine kinases, and subsequent activation of phospholipase C and protein kinase C. On the contrary, in hippocampal CA1 pyramidal neurons isolated from P7 rats, BDNF failed to occlude the GABA(B) receptor-mediated inhibition of GABA release. Thus, the ability of BDNF to occlude the GABA(B) receptor-mediated inhibition of GABA release develops between P7 and P14. This demonstrates a novel aspect of the effects of BDNF on inhibitory transmissions in rat hippocampus, which may have some functional roles in the induction of developmental plasticity and/or pathophysiology of epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Cells, Cultured
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / drug effects
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Patch-Clamp Techniques
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Protein Kinase C / metabolism
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism*
  • Rats
  • Rats, Wistar
  • Receptor, trkB / metabolism
  • Receptors, GABA-B / drug effects*
  • Signal Transduction / drug effects
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • GABA Agonists
  • GABA Antagonists
  • Receptors, GABA-B
  • Phorbol 12,13-Dibutyrate
  • gamma-Aminobutyric Acid
  • Receptor, trkB
  • Protein Kinase C