S.P. and H.B. contributed equally to this work.
Spontaneous glutamate release controls NT-3-dependent development of hippocampal calbindin–D28k phenotype through activation of sodium channels ex vivo
Article first published online: 6 JUN 2007
European Journal of Neuroscience
Volume 25, Issue 9, pages 2629–2639, May 2007
How to Cite
Pieraut, S., Boukhaddaoui, H., Scamps, F., Dayanithi, G., Sieso, V. and Valmier, J. (2007), Spontaneous glutamate release controls NT-3-dependent development of hippocampal calbindin–D28k phenotype through activation of sodium channels ex vivo. European Journal of Neuroscience, 25: 2629–2639. doi: 10.1111/j.1460-9568.2007.05534.x
- Issue published online: 6 JUN 2007
- Article first published online: 6 JUN 2007
- Received 28 November 2006, revised 8 March 2007, accepted 12 March 2007
- autocrine loop;
- ionotropic glutamate receptor;
- pyramidal neuron;
- spontaneous electrical activity
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–D28k 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–D28k-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–D28k 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.