Contribution of extrasynaptic NMDARs to bursting activity in nigral dopamine neurons

Movement initiation is preceded by bursting activity and increased dopamine release by substantia nigra pars compacta neurons. The participation of NMDARs is essential to the generation of bursts but the mechanisms regulating their level of activation are unknown. To examine the identity of the endogenous co-agonist implicated in the activation of NMDARs in mature dopamine neurons we used enzymatic depletion to reduce D-serine and glycine in ex vivo brain slices. We report that D-serine is predominant for the activation of synaptic NMDARs whereas glycine for extrasynaptic NMDARs. The burst pattern, which is mainly supported by extrasynaptic NMDARs, is insensitive to enzymatic treatment but glycine regulates their occurrence. While synaptic and extrasynaptic NMDARs are activated by distinct co-agonists their subunit composition is identical. This observations indicate that the compartmentalization of the co-agonist is not influenced by the expression of specific NMDAR subunits.