Electrophysiological and behavioral effects of group III metabotropic glutamate receptors on pallidal neurons in normal and parkinsonian rats

Abstract

The globus pallidus plays a critical role in movement regulation. Glutamate being an important excitatory neurotransmitter modulates the activity of pallidal neurons through both ionotropic and metabotropic glutamate receptors (mGluRs). Morphological studies have shown that group III mGluRs are generally located presynaptically in the globus pallidus. Up to now, little is known about the in vivo electrophysiological effects of group III mGluRs on the pallidal neurons. This study investigated the electrophysiological and behavioral effects of group III mGluRs on pallidal neurons in both normal and 6-hydroxydopamine (6-OHDA) lesioned parkinsonian rats. Micropressure ejection of group III mGluR agonist, L-2-amino-4-phosphonobutyrate (L-AP4), increased or decreased the firing rate of pallidal neurons in both normal and parkinsonian rats. The L-AP4-induced excitatory effects on the lesioned side of parkinsonian rats (117.4 ± 17.2%) were stronger than that in normal rats (64.3 ± 10.1%). While the proportion of neurons that were unresponsive to L-AP4 on the lesioned side of parkinsonian rats (50%) was more than that of normal rats (13%). Unilateral microinjection of L-AP4 into the globus pallidus induced a contralateral dystonic posturing in the presence of systemic haloperidol administration. The selective group III mGluRs antagonist, (RS)-α-cyclopropyl-4-phosphonophenylglycine, had no effect on pallidal neurons when used alone and could block both L-AP4-induced electrophysiological and behavioral effects. Combining electrophysiological and behavioral findings, we concluded that activation of group III mGluRs modulate the activity of pallidal neurons under both normal and parkinsonian state.