Orexin-A increases the activity of globus pallidus neurons in both normal and parkinsonian rats.

Orexin is a member of neuropeptides which was first identified in the hypothalamus. The globus pallidus is a key structure in the basal ganglia, which is involved in both normal motor function and movement disorders. Morphological studies have shown the expression of both OX1 and OX2 receptors in the globus pallidus. Employing single unit extracellular recordings and behavioural tests, the direct in vivo electrophysiological and behavioural effects of orexin-A in the globus pallidus were studied. Micro-pressure administration of orexin-A significantly increased the spontaneous firing rate of pallidal neurons. Correlation analysis revealed a negative correlation between orexin-A induced excitation and the basal firing rate. Furthermore, application of the specific OX1 receptor antagonist, SB-334867, decreased the firing rate of pallidal neurons, suggesting that endogenous orexinergic systems modulate the firing activity of pallidal neurons. Orexin-A increased the excitability of pallidal neurons through both OX1 and OX2 receptors. In 6-hydroxydopamine parkinsonian rats, orexin-A-induced increase in firing rate of pallidal neurons was stronger than that in normal rats. Immunostaining revealed positive OX1 receptor expression in the globus pallidus of both normal and parkinsonian rats. Finally, postural test showed that unilateral microinjection of orexin-A led to contralateral deflection in the presence of systemic haloperidol administration. Further elevated body swing test revealed that pallidal orexin-A and SB-334867 induced contralateral-biased swing and ipsilateral-biased swing respectively. Based on the electrophysiological and behavioural findings of orexin-A in the globus pallidus, the present findings may provide a rationale for the pathogenesis and treatment of Parkinson's disease.

Xue Y ，Yang YT ，Liu HY ，Chen WF ，Chen AQ ，Sheng Q ，Chen XY ，Wang Y ，Chen H ，Liu HX ，Pang YY ，Chen L ... -  《-》

The Subthalamic Neurons are Activated by Both Orexin-A and Orexin-B.

The subthalamic nucleus is an important nucleus in the indirect pathway of the basal ganglia circuit and therefore is involved in motor control under both normal and pathological conditions. Morphological studies reveal that the subthalamic nucleus receives relatively dense orexinergic projections originating from the hypothalamus. Both orexin-1 (OX1) and orexin-2 (OX2) receptors are expressed in the subthalamic nucleus. To explore the functions of orexinergic system in the subthalamic nucleus, extracellular electrophysiological recordings and behavioral tests were performed in the present study. Exogenous application of orexin-A significantly increased the spontaneous firing rate from 5.70 ± 0.66 Hz to 9.87 ± 1.18 Hz in 64.00% subthalamic neurons recorded. OX1 receptors are involved in orexin-A-induced excitation. Application of orexin-B increased the firing rate from 7.47 ± 0.92 Hz to 11.85 ± 1.39 Hz in 80.95% subthalamic neurons recorded, entirely through OX2 receptors. Both OX1 and OX2 receptor antagonists decreased the firing rate in 43.75% and 62.50% subthalamic neurons recorded respectively, suggesting the involvement of endogenous orexinergic system in the control of spontaneous firing activity. Further elevated body swing test revealed that microinjection of orexins and the receptor antagonists into the subthalamic nucleus induced contralateral-biased swing and ipsilateral-biased swing, respectively. Taken together, the present study suggests that orexins play important roles in the subthalamic nucleus which may provide further evidence for the involvement of subthalamic orexinergic tone in Parkinson's disease. Previous morphological studies indicate that the subthalamic nucleus receives orexinergic innervation and expresses both OX1 and OX2 receptors. Using in vivo multibarrel electrophysiological recordings, the present study revealed that exogenous application of orexin-A and orexin-B increased the spontaneous firing rate of the subthalamic neurons through OX1 and OX2 receptors. Endogenous orexinergic system was involved in the control of spontaneous firing of the subthalamic neurons. Further behavioral test revealed that intrasubthalamic application of orexins and the receptor antagonists induced biased swing behavior. The present study may provide further evidence for the involvement of subthalamic orexinergic tone in Parkinson's disease.

Sheng Q ，Xue Y ，Wang Y ，Chen AQ ，Liu C ，Liu YH ，Chu HY ，Chen L ... -  《-》

Orexins alleviate motor deficits via increasing firing activity of pallidal neurons in a mouse model of Parkinson's disease.

Wang Y ，Chen AQ ，Xue Y ，Liu MF ，Liu C ，Liu YH ，Pan YP ，Diao HL ，Chen L ... -  《-》

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

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.

Sun XR ，Chen L ，Chen WF ，Xue Y ，Yung WH ... -  《-》

Orexins increase the firing activity of nigral dopaminergic neurons and participate in motor control in rats.

Orexin is a member of neuropeptides which is involved in the central motor control. The substantia nigra pars compacta (SNc) is an important nucleus participating in motor control under both physiological and pathological conditions. Morphological studies reveal that orexinergic neurons located in lateral hypothalamus innervate the SNc. Both orexin-1 receptors (OX1 R) and orexin-2 receptors (OX2 R) are expressed in the SNc. To investigate the effects of orexins on SNc, single unit in vivo extracellular recordings and behavioral tests were performed in this study. Micro-pressure administration of orexin A and orexin B significantly increased the spontaneous firing rate of nigral DAergic neurons by 65.87 ± 7.73% and 90.49 ± 17.83%, respectively. The excitatory effects of orexin A on nigral DAergic neurons were mainly mediated by OX1 R, while OX2 R were involved in the increase in firing rate induced by orexin B. Selectively blocking OX1 R and OX2 R significantly decreased the firing rate of nigral DAergic neurons by 36.77 ± 6.26% and 32.04 ± 6.12%, respectively, which suggested that endogenous orexins modulated the spontaneous firing activity of nigral DAergic neurons. Finally, both elevated body swing test and haloperidol-induced postural behavioral test showed that unilateral microinjection of orexin A and orexin B induced significantly contralateral-biased swing and deflection behavior. Meanwhile, the specific OX1 R and OX2 R antagonists produced opposite effects. The present electrophysiological and behavioral studies suggested that orexins increased the firing activity of nigral DAergic neurons and participated in central motor control. Open Practices Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.

Liu C ，Xue Y ，Liu MF ，Wang Y ，Liu ZR ，Diao HL ，Chen L ... -  《-》