Extracellular glutamate concentration in hippocampal slice.

Synaptic glutamate transients resulting from vesicular exocytosis are superimposed on a low baseline concentration of glutamate in the extracellular space. Reported values of baseline glutamate concentrations range up to 4 microM. If glutamate were present tonically at low micromolar concentrations, many receptors, especially the high-affinity NMDA receptors (NMDARs), would be activated or desensitized, altering neuronal excitability. Using NMDARs expressed by CA1 pyramidal cells in acute hippocampal slices to monitor extracellular glutamate, we find that its baseline concentration is much lower, near 25 nM. In addition, superfusion of low micromolar concentrations of glutamate had no effect on neurons, indicating that glutamate transport prevents access to receptors within the slice. However, equipotent concentrations of NMDA, a nontransported agonist, depolarized neurons dramatically. We suggest that ambient concentrations of glutamate in vivo are also in the nanomolar range and are too low to cause significant receptor activation.