Differential subcellular localization of mGluR1a and mGluR5 in the rat andmonkey substantia nigra

Neurons in the rat substantia nigra (SN) are enriched in group I metabotrop ic glutamate receptor (mGluR) subtypes and respond to group I mGluR activat ion. To better understand the mechanisms by which mGluR1 and mGluR5 mediate these effects, the goal of this study was to elucidate the subsynaptic loc alization of these two receptor subtypes in the rat and monkey substantia n igra. At the light microscope level, neurons of the SN pars reticulata (SNr ) displayed moderate to strong immunoreactivity for both mGluR1a and mGluR5 in rats and monkeys. However, mGluR1a labeling was much stronger in monkey than in rat SN pars compacta (SNc) neurons, whereas a moderate level of mG luR5 immunoreactivity was found in both species. At the electron microscope level, the immunoreactivity for both group I mGluR subtypes was primarily expressed postsynaptically, although light mGluR1a labeling was occasionall y seen in axon terminals in the rat SNr. Immunogold studies revealed a stri king difference in the subcellular distribution of mGluR1a and mGluR5 immun oreactivity in SNr and SNc neurons. Although the bulk of mGluR1a was attach ed to the plasma membrane, >80% of mGluR5 immunoreactivity was intracellula r. Plasma membrane-bound immunoreactivity for group I mGluRs in both SNc an d SNr neurons was mostly extrasynaptic or in the main body of symmetric, pu tative GABAergic synapses. On the other hand, asymmetric synapses either we re nonimmunoreactive or displayed perisynaptic labeling. These data raise i mportant questions about the trafficking, internalization, and potential fu nctions of group I mGluRs at extrasynaptic sites or symmetric synapses in t he substantia nigra.