l-Glutamate excitation of A10 dopamine neurons is preferentially mediated by activation of NMDA receptors: extra- and intracellular electrophysiological studies in brain slices

The aim of the present study was to assess the effects of l-glutamate (l-GLU) on the neurophysiology of ventral tegmental A10 dopamine neurons in rat midbrain slices using extracellular and intracellular recording methods. l-Glutamate perfusion of 10-100 μM concentrations produced dose-dependent increases in firing rate, with no changes in pattern of firing, while higher concentrations led to a loss of activity reminiscent of depolarization inactivation. The extracellular changes were relfected by the pronounced membrane depolarizations observed through intracellular recordings. The effects of low doses (≦ 30 μM) of l-GLU on firing rate and membrane potential were completely antagonized by co-perfusion with the noncompetitive NMDA blocker, phencyclidine, or the selective competitive NMDA receptor antagonist, CGS 19755, but not by the selective non-NMDA blocker NBQX. However, at concentrations of ≧ 300 μM l-GLU's effects could not be completely blocked without the presence of both CGS 19755 and NBQX. Moreover, the magnitude of l-GLU-induced depolarizations became attenuated at membrane potentials more negative than -70 mV. These results suggest that in physiological-like conditions that low extracellular levels of glutamate excite midbrain dopamine neurons via a preferential activation of NMDA receptors, and that only at higher concentrations of l-GLU are non-NMDA receptors brought into play.