| The globus pallidus (GP) is an important structure in the basal ganglia circuit, which plays key roles in physiological movement regulation and the pathogenesis of basal ganglia disorders such as Parkinson’s disease. Glutamate is one of the most essential excitatory neurotransmitters in the central nervous systems. Besides the ionotropic receptors, glutamate also acts on the metabotropic glutamate receptors (mGluRs). The inhibition of glutamatergic transmission may be important to alleviate parkinsonian symptoms and mGluRs could modulate glutamate neurotransmission. Therefore, the function and the relevance between mGluRs and neurodegenerative diseases received more and more attention nowadays. Morphological studies have revealed that all sorts of mGluRs are expressed in the globus pallidus and functional investigations indicated that the antagonists of group I mGluRs or some agonists of group III mGluRs may possess antiparkinsonian properties.Object:To investigate the electrophysiological and behavioral effects and possible mechanism of group I and III mGluRs on the globus pallidus in both normal and 6-hydroxydopamine (6-OHDA) lesioned parkinsonian rats.Methods:Extracellular recording in vivo, immunohistochemical technique and behavioral tests were used in our study.Results:1. Electrophysiological effects of group I mGluRs in the globus pallidus:1) In normal rats, DHPG, a selective group I mGluRs receptor agonist, could increase the firing rate of pallidal neurons. LY 367385, a selective mGluRl receptor antagonist, had no significant effect on pallidal neurons. However, MPEP, a selective mGluR5 receptor antagonist, increased the firing rate of pallidal neurons. The DHPG-induced excitatory effect could be blocked by LY367385 but not MPEP.2) On the lesioned side of 6-OHDA parkinsonian rats, DHPG increased the firing rate of pallidal neurons. The DHPG-induced excitation was significantly weaker than that in normal rats. LY367385 had no obvious effect on pallidal neurons but MPEP increased the firing rate of pallidal neurons. Neither LY367385 nor MPEP could block the excitatory effect induced by DHPG.3) On the unlesioned side of 6-OHDA parkinsonian rats, DHPG increased the firing rate of pallidal neurons. This excitatory effect was similar to that of normal rats but stronger than that of lesioned side. LY367385 had no obvious effect on pallidal neurons but MPEP decreased the firing rate of pallidal neurons. The excitatory effect induced by DHPG could not be blocked by LY367385 but could be blocked by MPEP.4) There is no correlation between DHPG-induced excitation and the basal firing rate of pallidal neurons in normal rats. But a negative correlation between them was observed in 6-OHDA lesioned parkinsonian rats.2. The immunohistochemical staining showed that the expression of mGluRla decreased in the globus pallidus of both lesioned and unlesioned side of pakinsonian rats. Furthermore, the decrease of mGluRla expression was greater on unlesioned side. The expression of mGluR5 had no obvious change.3. In the behaving test, unilateral microinjection of DHPG into the globus pallidus induced a contralateral dystonic posturing in the presence of systemic haloperidol administration. This effect could be blocked by LY367385 but not MPEP.4. Electrophysiological effects of groupⅢmGluRs in the globus pallidus:1) L-AP4, a selective groupⅢmGluRs receptor agonist, had excitatory or inhibitory effect on pallidal neurons and more neurons showed excitatory response. The L-AP4-induced effects could be blocked by CPPG, which is a selective groupⅢmGluRs antagonist.2) On the lesioned side of parkinsonian rats, the excitatory effect produced by L-AP4 was much stronger than that of normal rats and unlesioned side. The L-AP4-induced excitation on the unlesioned side of parkinsonian rats tends to be decreased although there was no statistic difference.5. In the behaving test, unilateral microinjection of L-AP4 into the globus pallidus induced a contralateral dystonic posturing in the presence of systemic haloperidol administration. This effect could be blocked by CPPG.Conclusion:Activation of groupⅠmGluRs produces excitatory effects on globus pallidus neurons via mGluR1 in normal rats, and probably via both mGluRl and mGluR5 in 6-OHDA lesioned parkinsonian rats. The excitatory effect of DHPG on pallidal neurons may decrease under parkinsonian state due to the reduced expression of mGluRla in the globus pallidus. Activation of group III mGluRs mainly produced excitatory effect on globus pallidus neurons and this effect was more stronger in parkinsonian state. The present study may provide a rationale for further investigations into the potential of pallidal mGluRs system in the pathogenesis and treatment of Parkinson’s disease. |
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