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

Abstract

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 (OX R) and orexin-2 receptors (OX 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 OX R, while OX R were involved in the increase in firing rate induced by orexin B. Selectively blocking OX R and OX 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 OX R and OX 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/.

Orexin-A Exerts Neuroprotective Effects via OX1R in Parkinson’s Disease

“…We interpreted that the increased spontaneous physical activity of orexin-A treatment on day 1 might be partially associated with the direct excitatory effect of orexin-A on some motor function associated central neurons, while the prolonged motor improvement is probably due to its neuroprotection on dopaminergic neurons in SNpc. Consistently, our recent published work confirmed that orexin-A increases the spontaneous firing rate of dopaminergic neurons in the SNpc ( Liu C. et al, 2018 ).…”

Orexin A as a modulator of dorsal lateral geniculate neuronal activity: a comprehensive electrophysiological study on adult rats

“…OXs are generally considered excitatory in both in vivo and in vitro preparations. Excitation of spontaneous neuronal activity by OXs has been observed under urethane anaesthesia in the hippocampus 62 , globus pallidus 74 , substantia nigra pars compacta 63 , dorsal raphe (DRN) 75 and laterodorsal tegmental nucleus (LTD) 64 . Moreover, increases in neuronal activity in vitro upon OX application have been showed in numerous brain structures, such as the locus coeruleus 76,77 , tuberomammillary nucleus 78 , DRN 79 , intergeniculate leaflet 59,80 and paraventricular nucleus of the thalamus 61 .…”

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

“…Orexin neurons located predominantly in the perifornical area and lateral hypothalamus exert important roles through wide projection in the central nervous system. Endogenous orexins modulate the firing activity of dopaminergic neurons in the substantia nigra pars compacta (38). Orexin knockout mice show sex-and age-related changes in insulin resistance (51,60).…”