Postnatal changes in somatic gamma-aminobutyric acid signalling in the rat hippocampus

Eur J Neurosci. 2008 May;27(10):2515-28. doi: 10.1111/j.1460-9568.2008.06234.x.

Abstract

During postnatal development of the rat hippocampus, gamma-aminobutyric acid (GABA) switches its action on CA3 pyramidal cells from excitatory to inhibitory. To characterize the underlying changes in the GABA reversal potential, we used somatic cell-attached recordings of GABA(A) and N-methyl-D-aspartate channels to monitor the GABA driving force and resting membrane potential, respectively. We found that the GABA driving force is strongly depolarizing during the first postnatal week. The strength of this depolarization rapidly declines with age, although GABA remains slightly depolarizing, by a few millivolts, even in adult neurons. Reduction in the depolarizing GABA driving force was due to a progressive negative shift of the reversal potential of GABA currents. Similar postnatal changes in GABA signalling were also observed using the superfused hippocampus preparation in vivo, and in the hippocampal interneurons in vitro. We also found that in adult pyramidal cells, somatic GABA reversal potential is maintained at a slightly depolarizing level by bicarbonate conductance, chloride-extrusion and chloride-loading systems. Thus, the postnatal excitatory-to-inhibitory switch in somatic GABA signalling is associated with a negative shift of the GABA reversal potential but without a hyperpolarizing switch in the polarity of GABA responses. These results also suggest that in adult CA3 pyramidal cells, somatic GABAergic inhibition takes place essentially through shunting rather than hyperpolarization. Apparent hyperpolarizing GABA responses previously reported in the soma of CA3 pyramidal cells are probably due to cell depolarization during intracellular or whole-cell recordings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Animals
  • Animals, Newborn
  • Cell Differentiation / physiology*
  • Cell Membrane / drug effects
  • Cell Membrane / physiology
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism
  • Hippocampus / cytology
  • Hippocampus / growth & development*
  • Hippocampus / metabolism*
  • Interneurons / cytology
  • Interneurons / drug effects
  • Interneurons / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism
  • Rats
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Chloride Channels
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • gamma-Aminobutyric Acid