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Orexin is exclusively produced in neurons localized within the lateral hypothalamic area (LHA) and perifornical area (PFA). Orexin has been identified as a key promotor of arousal. The selective loss of orexinergic neurons results in narcolepsy. It is known that the intrinsic electrophysiological properties are critical for neurons to perform their functions in corresponding brain regions. In addition to hypothalamic orexin, other brain nuclei are involved in the regulation of sleep and wakefulness. Quite a lot of studies focus on elucidating orexin‐induced regulation of sleep–wake states and modulation of neuronal electrophysiological properties in several brain regions. Here, we summarize that the orexinergic neurons exhibit spontaneous firing activity which is associated with the states of sleep–wake cycle. Orexin mainly exerts postsynaptic excitatory effects on multiple brain nuclei associated with the process of sleep and wakefulness. This review may provide a background to guide future research about the cellular mechanisms of orexin‐induced maintaining of arousal. [ABSTRACT FROM AUTHOR]

The glucagon-like peptide-1 (GLP-1) plays important roles in the regulation of food intake and energy metabolism. Peripheral or central GLP-1 suppresses food intake and reduces body weight. The electrophysiological properties of neurons in the mammalian central nervous system reflect the neuronal excitability and the functional organization of the brain. Recent studies focus on elucidating GLP-1-induced suppression of feeding behaviors and modulation of neuronal electrophysiological properties in several brain regions. Here, we summarize that activation of GLP-1 receptor (GLP-1R) suppresses food intake and induces postsynaptic depolarization of membrane potential and/or presynaptic modulation of glutamatergic or GABAergic neurotransmission in brain nuclei located within the medulla oblongata, pons, mesencephalon, diencephalon, and telencephalon. This review may provide a background to guide future research about the cellular mechanisms of GLP-1-induced feeding inhibition. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: The paraventricular nucleus (PVN) of hypothalamus is a major integrative center in homeostatic control. Morphological studies have revealed a high level of secretin and secretin receptor expression in the PVN. To investigate the direct electrophysiological effects of secretin in the PVN, in vivo extracellular recordings were performed in the present study. In 24 out of the 46 paraventricular neurons, micro-pressure ejection of secretin increased the firing rate from 3.07±0.43Hz to 4.86±0.70Hz. In another 8 out of the 46 paraventricular neurons, secretin decreased the firing rate from 2.61±0.46Hz to 1.41±0.25Hz. In the remaining 14 paraventricular neurons, secretin did not alter the firing rate significantly. The present findings provided direct electrophysiological evidence for the possible functions of secretin in the PVN. [Copyright &y& Elsevier]

The dopaminergic neurons in the substantia nigra pars compacta are characterized by autonomous pacemaking activity. The spontaneous firing activity of nigral dopaminergic neurons plays an important role in physiological function and is essential for their survival. Importantly, the spontaneous firing activity may also be involved in the preferential vulnerability of the nigral dopaminergic neurons in Parkinson's disease (PD). The neuropeptide apelin was reported to exert neuroprotective effects in neurodegenerative diseases, including PD. And it was noticed that apelin modulates neuronal activity in some brain regions. The present study investigated the electrophysiological and behavioral effects of apelin in the substantia nigra. Double-labeling immunofluorescence showed that apelin was present in nigral dopaminergic neurons and that these neurons expressed apelin receptor APJ. Further single unit in vivo electrophysiological recordings revealed that endogenous apelin tonically increased the firing rate of nigral dopaminergic neurons in both normal and parkinsonian animals. Exogenous apelin-13 exerted excitatory effects on the majority of nigral dopaminergic neurons, yet reduced excitability in a subset of neurons. In addition, nigral application of apelin-13 increased motor activity in normal rats and blocking endogenous apelin reduced motor activity. Considering the involvement of the spontaneous firing activity of nigral dopaminergic neurons in the development of PD and the possibility that apelin acts in an autocrine manner on apelin receptors expressed by nigral dopaminergic neurons, the modulation of the spontaneous firing activity of nigral dopaminergic neurons by apelin may serve as a neuroprotective factor in PD. • Apelin and APJ were colocalized with TH in the nigral dopaminergic neurons. • Endogenous apelin modulated the firing activity of nigral dopaminergic neurons. • Apelin-13 bidirectionally regulated the excitability of nigral dopaminergic neurons. • Apelin in SNc enhanced motor activity of normal rats. [ABSTRACT FROM AUTHOR]

The globus pallidus plays a significant role in motor control under both health and pathological states. Recent studies have revealed that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels occupy a critical position in globus pallidus pacemaking activity. Morphological studies have shown the expression of HCN channels in the globus pallidus. To investigate the in vivo effects of HCN channels in the globus pallidus, extracellular recordings and behavioral tests were performed in the present study. In normal rats, micro-pressure ejection of 0.05 mM ZD7288, the selective HCN channel blocker, decreased the frequency of spontaneous firing in 21 out of the 40 pallidal neurons. The average decrease was 50.4 ± 5.4%. Interestingly, in another 18 out of the 40 pallidal neurons, ZD7288 increased the firing rate by 137.1 ± 27.6%. Similar bidirectional modulation on the firing rate was observed by a higher concentration of ZD7288 (0.5 mM) as well as another HCN channel blocker, CsCl. Furthermore, activation of HCN channels by 8-Br-cAMP increased the firing rate by 63.0 ± 9.3% in 15 out of the 25 pallidal neurons and decreased the firing rate by 46.9 ± 9.4% in another 8 out of the 25 pallidal neurons. Further experiments revealed that modulation of glutamatergic but not GABAergic transmission may be involved in ZD7288-induced increase in firing rate. Consistent with electrophysiological results, further studies revealed that modulation of HCN channels also had bidirectional effects on behavior. Taken together, the present studies suggest that HCN channels may modulate the activity of pallidal neurons by different pathways in vivo . [ABSTRACT FROM AUTHOR]