La sous-saturation du site de la glycine des récepteurs NMDA permet la régulation de l'activité en bouffée dans les neurones à dopamine de la substance noire compacte de rat juvénile

peer reviewedThe activation of N-methyl-D-aspartate receptors (NMDARs) in substantia nigra pars compacta (SNc) dopamine (DA) cells is central to generate the bursting activity, a phasic signal linked to DA related behaviors via the change in postsynaptic DA release. NMDARs are recruited during excitatory synaptic transmission by glutamate release but the glycine site level of occupancy of these receptors during basal action potential-dependent activity is not known for SNc DA neurons. We explored NMDARdependent signals during exogenous applications of co-agonists in midbrain slices from juvenile rats. We found that both glycine and D-serine strengthened the NMDAR-dependent component of excitatory postsynaptic currents (EPSCs) in a concentration-dependent manner. EPSCs were also increased by endogenous glycine via the blockade of the glycine transport. The glycine site of NMDARs contributing to synaptic transmission is therefore subsaturated. The behaviorally relevant burst firing was more sensitive to exogenous D-serine and endogenous glycine than to exogenous glycine. The mechanisms regulating the availability of the co-agonists exert consequently a critical influence on the excitability of DA neurons via NMDARs. The modulation of the phasic firing in DA neurons by ambient NMDAR co-agonists may be important for nigral information processing and downstream motor-related behavior.Physiology of dopaminergic neuron