Differential NMDA-dependent activation of glial cells in mouse hippocampus.
In the hippocampus, the NMDA receptor is thought to be an important glutamate receptor involved in synaptic plasticity and in memory processes. Until recently, NMDA receptors have been considered solely as neuronal components, but some evidence suggests that glial cells in the hippocampus, and in particular astrocytes, also could be activated by NMDA applications. On the basis of their shape and electrophysiological properties (linear and rectified I/V curve), we describe two different populations of glial cells from GFAP-GFP transgenic mice that are activated differentially by NMDA. We found that linear glial cells were depolarized by NMDA that was not dependent on Ca2+ rise but partially involved a Ca2+ entry. Additionally, NMDA-induced depolarization of linear glial cells involved both a TTX-independent pathway likely through a direct activation, and a TTX-dependent pathway that required neuronal activity. The NMDA-induced depolarization in these cells was in part due to the activation of glutamate transporters and GABA B receptors. Furthermore, TTX-dependent NMDA-induced activation regulates the level of gap junction coupling between linear glial cells. In contrast, NMDA-induced depolarization in outward rectifying cells do not require a Ca2+ rise but are mediated directly by Ca2+ entry and are independent of glutamate transporters, GABA B and GABA A receptors. Our findings reveal that NMDA differentially activates hippocampal glial cells and the glial network through heterogeneous mechanisms in a cell-type specific manner.
Serrano
Alexandre
A
Groupe de Recherche sur le Système Nerveux Central et Département de Physiologie, Université de Montréal, Succursale Centre-Ville, Montréal, Québec, Canada.
Robitaille
Richard
R
Lacaille
Jean-Claude
JC
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D050496:Vesicular Glutamate Transport Proteins / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D018690:Excitatory Amino Acid Agonists; D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; D026941:Sodium Channel Blockers; D050496:Vesicular Glutamate Transport Proteins; D013779:Tetrodotoxin; D016202:N-Methylaspartate; D002118:Calcium