Adenosine A2A Receptor Modulates the Activity of Globus Pallidus Neurons 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 (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/.

show abstract

“…; Diao et al . ). Microinjection of orexins into the SNc improved catalepsy and akinesia caused by haloperidol.…”

Section: Discussionmentioning

confidence: 97%

“…), while behavioral test was determined based on that of previous studies (Diao et al . ; Xue et al . ).…”

Section: Methodsmentioning

confidence: 99%

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

Liu

Xue

Liu

et al. 2018

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The sample size for the present in vivo electrophysiological recordings was determined by pilot studies according to the formula for paired samples (58), and that for the behavioral test was based on that of previous studies (11,66). The data are expressed as means Ϯ SE.…”

Section: Methodsmentioning

confidence: 99%

“…The basal firing rate of globus pallidus neurons in MPTP parkinsonian mice was slower than that in control mice (control: 6.60 Ϯ 0.44 Hz, n ϭ 89; MPTP: 5.27 Ϯ 0.40 Hz, n ϭ 62; t ϭ 2.150, P ϭ 0.033). In our previous electrophysiological recordings (11), three firing patterns, regular, irregular, and bursting, were recorded in pallidal neurons of rats. These three firing patterns of globus pallidus neurons were also observed in the present recordings of mice.…”

Section: Bilateral Pallidal Injection Of Orexin-a and Orexin-b Increased Locomotor Activity In Mptp Parkinsonian Micementioning

confidence: 99%

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

Wang

Chen

Xue

et al. 2019

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

Orexin is a peptide neurotransmitter released in the globus pallidus. Morphological evidence reveals that both orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) exist in the globus pallidus. Here we showed that bilateral microinjection of both orexin-A and orexin-B into the globus pallidus alleviated motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice. Further in vivo extracellular single-unit recording revealed that the basal spontaneous firing rate of the globus pallidus neurons in MPTP parkinsonian mice was slower than that of normal mice. Application of orexin-A or orexin-B significantly increased the spontaneous firing rate of pallidal neurons. The influx of Ca2+ through the L-type Ca2+ channel is the major mechanism involved in orexin-induced excitation in the globus pallidus. Orexin-A-induced increase in firing rate of pallidal neurons in MPTP parkinsonian mice was stronger than that of normal mice. Orexin-A exerted both electrophysiological and behavioral effects mainly via OX1R, and orexin-B exerted the effects via OX2R. Endogenous orexins modulated the excitability of globus pallidus neurons mainly through OX1R. The present behavioral and electrophysiological results suggest that orexins ameliorate parkinsonian motor deficits through increasing the spontaneous firing of globus pallidus neurons.

show abstract

“…The main synaptic input to the GP is provided by a sub-population of GABAergic striatal neurons that preferentially express dopamine D 2 receptors and enkephalins [5]. These neurons also express high levels of A 2A Rs [7], coupled to Gα s proteins and thus to the adenosine 3′,5′-cyclic monophosphate (cAMP)/PKA pathway [8], and whose activation facilitates GABA release in rat GP [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Adenosine A2A and histamine H3 receptors interact at the cAMP/PKA pathway to modulate depolarization-evoked [3H]-GABA release from rat striato-pallidal terminals

Morales-Figueroa

Rivera-Ramírez

González-Pantoja

et al. 2018

Purinergic Signalling

View full text Add to dashboard Cite

We previously reported that the activation of histamine H 3 receptors (H 3 Rs) selectively counteracts the facilitatory action of adenosine A 2A receptors (A 2A Rs) on GABA release from rat globus pallidus (GP) isolated nerve terminals (synaptosomes). In this work, we examined the mechanisms likely to underlie this functional interaction. Three possibilities were explored: (a) changes in receptor affinity for agonists induced by physical A 2A R/H 3 R interaction, (b) opposite actions of A 2A Rs and H 3 Rs on depolarization-induced Ca 2+ entry, and (c) an A 2A R/H 3 R interaction at the level of adenosine 3′,5′-cyclic monophosphate (cAMP) formation. In GP synaptosomal membranes, H 3 R activation with immepip reduced A 2A R affinity for the agonist 2-p-(2-carboxyethyl)phenethylamino-5′-Nethylcarboxamidoadenosine hydrochloride hydrate (CGS-21680) (K i control 4.53 nM; + immepip 9.32 nM), whereas A 2A R activation increased H 3 R affinity for immepip (K i control 0.63 nM; + CGS-21680 0.26 nM). Neither A 2A R activation nor H 3 R stimulation modified calcium entry through voltage-gated calcium channels in GP synaptosomes, as evaluated by microfluorometry. A 2A Rmediated facilitation of depolarization-evoked [2,3-3 H]-γ-aminobutyric acid ([ 3 H]-GABA) release from GP synaptosomes (130.4 ± 3.6% of control values) was prevented by the PKA inhibitor H-89 and mimicked by the adenylyl cyclase activator forskolin or by 8-Bromo-cAMP, a membrane permeant cAMP analogue (169.5 ± 17.3 and 149.5 ± 14.5% of controls). H 3 R activation failed to reduce the facilitation of [ 3 H]-GABA release induced by 8-Bromo-cAMP. In GP slices, A 2A R activation stimulated cAMP accumulation (290% of basal) and this effect was reduced (− 75%) by H 3 R activation. These results indicate that in striato-pallidal nerve terminals, A 2A Rs and H 3 Rs interact at the level of cAMP formation to modulate PKA activity and thus GABA release.

show abstract

Adenosine A2A Receptor Modulates the Activity of Globus Pallidus Neurons in Rats

Cited by 10 publications

References 59 publications

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

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

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

Adenosine A2A and histamine H3 receptors interact at the cAMP/PKA pathway to modulate depolarization-evoked [3H]-GABA release from rat striato-pallidal terminals

Contact Info

Product

Resources

About