Spontaneous glutamate release controls NT-3-dependent development of hippocampal calbindin-D(28k) phenotype through activation of sodium channels ex vivo

Eur J Neurosci. 2007 May;25(9):2629-39. doi: 10.1111/j.1460-9568.2007.05534.x.


Functional NMDA and AMPA ionotropic glutamate receptors are expressed in embryonic hippocampal glutamatergic pyramidal neurons prior to synapse formation but their function and mechanisms of action are still unclear. At the same time, these neurons develop their calbindin-D(28k) phenotype through an activity-dependent NT-3 autocrine loop. Using single-neuron microcultures, we show here that immature pyramidal neurons spontaneously secreted glutamate and that chronic blockade of either NMDA or AMPA receptors down-regulated the number of calbindin-D(28k)-positive pyramidal neurons without affecting neuronal survival. This antagonistic effect of glutamate ionotropic receptors was mimicked by anti-TrkC antibodies and reversed by the application of NT-3. Similar results were obtained in ex vivo embryonic hippocampal slice cultures. Moreover, glutamate receptor blockade inhibited the generation of spontaneous sodium-driven action potentials which, in turn, regulate both the endogenous secretion of NT-3 and the calbindin-D(28k) phenotype acquisition. Altogether, these results suggest an unexpected role for glutamate in the development of the physiological and biochemical properties of hippocampal pyramidal neurons and support the idea that glutamate may underlie an activity-dependent mode of differentiation prior to synapse formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Calbindins
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Membrane / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism*
  • Hippocampus / embryology*
  • Neurotrophin 3 / metabolism*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Phenotype
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkC / antagonists & inhibitors
  • Receptor, trkC / metabolism
  • Receptors, Glutamate / drug effects
  • Receptors, Glutamate / metabolism
  • S100 Calcium Binding Protein G / metabolism*
  • Sodium Channels / metabolism*
  • Synapses / drug effects
  • Synapses / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology


  • Calbindins
  • Excitatory Amino Acid Antagonists
  • Neurotrophin 3
  • Receptors, Glutamate
  • S100 Calcium Binding Protein G
  • Sodium Channels
  • Glutamic Acid
  • Receptor, trkC