Low concentrations of alcohol inhibit BDNF-dependent GABAergic plasticity via L-type Ca2+ channel inhibition in developing CA3 hippocampal pyramidal neurons

J Neurosci. 2010 May 12;30(19):6776-81. doi: 10.1523/JNEUROSCI.5405-09.2010.

Abstract

Fetal alcohol spectrum disorder (FASD) is associated with learning and memory alterations that could be, in part, a consequence of hippocampal damage. The CA3 hippocampal subfield is one of the regions affected by ethanol (EtOH), including exposure during the third trimester-equivalent (i.e., neonatal period in rats). However, the mechanism of action of EtOH is poorly understood. In CA3 pyramidal neurons from neonatal rats, dendritic BDNF release causes long-term potentiation of the frequency of GABAA receptor-mediated spontaneous postsynaptic currents (LTP-GABAA) and this mechanism is thought to play a role in GABAergic synapse maturation. Here, we show that short- and long-term exposure of neonatal male rats to low EtOH concentrations abolishes LTP-GABAA by inhibiting L-type voltage-gated Ca2+ channels. These findings support the recommendation that even light drinking should be avoided during pregnancy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain-Derived Neurotrophic Factor / metabolism
  • CA3 Region, Hippocampal / drug effects*
  • CA3 Region, Hippocampal / growth & development
  • CA3 Region, Hippocampal / physiology
  • Calcium Channels, L-Type / metabolism
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / pharmacology*
  • Ethanol / administration & dosage
  • Ethanol / pharmacology*
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Long-Term Potentiation / physiology
  • Male
  • Pyramidal Cells / drug effects*
  • Pyramidal Cells / growth & development
  • Pyramidal Cells / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / metabolism
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Calcium Channels, L-Type
  • Central Nervous System Depressants
  • Receptors, GABA-A
  • Ethanol
  • gamma-Aminobutyric Acid