GABA actions in hippocampal area CA3 during postnatal development: differential shift from depolarizing to hyperpolarizing in somatic and dendritic compartments

J Neurophysiol. 2008 Mar;99(3):1523-34. doi: 10.1152/jn.01074.2007. Epub 2008 Jan 23.


Gamma-aminobutyric acid type A receptor (GABA(A)-R) activation leads to depolarization of pyramidal cells during the first postnatal week and produces hyperpolarization from the second week. However, immunohistochemical evidence has suggested that during the second and third postnatal weeks the NKCC1 cotransporter relocates from the soma to the dendrites of CA3 pyramidal cells. We hypothesized that this leads to depolarizing responses in apical dendrites. Here we show that the activation of GABA(A)-R in the distal dendrites of CA3 pyramidal cells at P15 by restricted application of muscimol or synaptic activation by stimulation of interneurons in stratum radiatum (SR) causes depolarizing postsynaptic potentials (PSPs), which are blocked by NKCC1 cotransporter antagonists. By contrast, activation of proximal GABA(A)-R by muscimol application or by stimulation of interneurons in s. oriens (SO) leads to hyperpolarizing PSPs. Activation of the dentate gyrus (DG) in the presence of glutamatergic blockers evokes hyperpolarizing responses during the second postnatal week; however, the reversal potential of the DG-evoked inhibitory (I)PSPs is more depolarized than that of IPSPs evoked by activation of SO interneurons. Despite the shift of GABA action from depolarizing to hyperpolarizing, DG-evoked field potentials (f-PSPs) recorded in s. lucidum/radiatum (SL/R) do not change in polarity until the third week. Current source density analysis yielded results consistent with depolarizing actions of GABA in the dendritic compartment. Our data suggest that GABAergic input to apical dendrites of pyramidal cells of CA3 evokes depolarizing PSPs long after synaptic inhibition has become hyperpolarizing in the somata, in the axon initial segments and in basal dendrites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Dendrites / drug effects
  • Dendrites / physiology*
  • Dose-Response Relationship, Radiation
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • GABA Agonists / pharmacology*
  • GABA Antagonists / pharmacology
  • Hippocampus / cytology*
  • Hippocampus / growth & development*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Muscimol / pharmacology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neural Inhibition / radiation effects
  • Neurons / cytology*
  • Neurons / drug effects
  • Patch-Clamp Techniques
  • Pyridazines / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Wistar
  • Valine / analogs & derivatives
  • Valine / pharmacology
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / physiology*


  • Excitatory Amino Acid Antagonists
  • GABA Agonists
  • GABA Antagonists
  • Pyridazines
  • Quinoxalines
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Muscimol
  • gamma-Aminobutyric Acid
  • 2-amino-5-phosphopentanoic acid
  • gabazine
  • Valine