GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex in primates

Abstract

Glutamate and GABA neurotransmission is mediated through various types of ionotropic and metabotropic receptors. In this review, we summarise some of our recent findings on the subcellular and subsynaptic localisation of GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex of monkeys. Polyclonal antibodies that specifically recognise GABA_BR1, mGluR1a and mGluR5 receptor subtypes were used for immunoperoxidase and pre-embedding immunogold techniques at the light and electron microscope levels. Both subtypes of group I mGluRs were expressed postsynaptically in striatal projection neurons and interneurons where they aggregate perisynaptically at asymmetric glutamatergic synapses and symmetric dopaminergic synaptic junctions. Moreover, they are also strongly expressed in the main body of symmetric synapses established by putative intrastriatal GABAergic terminals. In the globus pallidus, both receptor subtypes are found postsynaptically in the core of striatopallidal GABAergic synapses and perisynaptically at subthalamopallidal glutamatergic synapses. Finally, extrasynaptic labelling was commonly seen in the globus pallidus and the striatum.

Moderate to intense GABA_BR1 immunoreactivity was observed in the striatopallidal complex. At the electron microscope level, GABA_BR1 immunostaining was commonly found in neuronal cell bodies and dendrites. Many striatal dendritic spines also displayed GABA_BR1 immunoreactivity. Moreover, GABA_BR1- immunoreactive axons and axon terminals were frequently encountered. In the striatum, GABA_BR1- immunoreactive boutons resembled terminals of cortical origin, while in the globus pallidus, subthalamic-like terminals were labelled. Pre-embedding immunogold data showed that postsynaptic GABA_BR1 receptors are concentrated at extrasynaptic sites on dendrites, spines and somata in the striatopallidal complex, perisynaptically at asymmetric synapses and in the main body of symmetric striatopallidal synapses in the GPe and GPi. Consistent with the immunoperoxidase data, immunoparticles were found in the presynaptic grid of asymmetric synapses established by cortical- and subthalamic-like glutamatergic terminals.

These findings indicate that both GABA and glutamate metabotropic receptors are located to subserve various modulatory functions of the synaptic transmission in the primate striatopallidal complex. Furthermore, their pattern of localisation raises issues about their roles and mechanisms of activation in normal and pathological conditions. Because of their ‘modulatory’ functions, these receptors are ideal targets for chronic drug therapies in neurodegenerative diseases such as Parkinson's disease.