Modulation of AMPA currents by D1-like but not D2-like receptors in spinal motoneurons

Han, Pengcheng; Whelan, Patrick J.

doi:10.1016/j.neuroscience.2008.11.040

Cited by 38 publications

(39 citation statements)

References 46 publications

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“…As shown in Figure 2 A, neither the D1-like receptor antagonist LE300 [10 nM (Han and Whelan, 2009) Alberto et al, 2006)] individually or in combination inhibited the DA effect. Moreover, a mixture of D1-and D2-like receptor agonists SKF81297 (10 M) and quinpirole (50 M), respectively, failed to induce an outward current.…”

Section: Resultsmentioning

confidence: 95%

Dopamine Acts as a Partial Agonist for 2A Adrenoceptor in Melanin-Concentrating Hormone Neurons

Alberto¹,

Trask²,

Hirasawa³

2011

Journal of Neuroscience

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Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that promotes positive energy balance and anxiety. Since dopamine (DA) is also closely implicated in these functions, the present study investigated the effect of DA on MCH neurons. Using whole-cell patch-clamp recordings in rat brain slices, we found that DA hyperpolarizes MCH neurons by activating G-protein-activated inwardly rectifying K ϩ (GIRK) channels. Pharmacological study indicated that the effect was mediated by ␣2A adrenoceptors, not DA receptors. DA-induced outward current was also observed in the presence of tetrodotoxin or the dopamine ␤-hydroxylase inhibitor fusaric acid, suggesting that DA directly binds to ␣2A receptors on MCH neurons, rather than acting presynaptically or being transformed into norepinephrine (NE) in the slice preparation. The effects of NE and DA were concentration-dependent with EC 50 of 5.9 and 23.7 M, respectively, and a maximal effect of 106.6 and 57.2 pA, respectively, suggesting that DA functions as a partial agonist. Prolonged (5 min) activation of ␣2A receptors by either DA or NE attenuated the subsequent response to DA or NE, while 5 s applications were not sufficient to induce desensitization. Therefore, a history of ␣2A receptor activation by DA or NE can have a lasting inhibitory effect on the catecholaminergic transmission to MCH neurons. Our study suggests that ␣2A receptors expressed by MCH neurons may be one of the pathways by which DA and NE can interact and modulate mood and energy homeostasis, and this cross talk may have functional implications in mood disorders and obesity.

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Section: Resultsmentioning

confidence: 95%

Dopamine Acts as a Partial Agonist for 2A Adrenoceptor in Melanin-Concentrating Hormone Neurons

Alberto¹,

Trask²,

Hirasawa³

2011

Journal of Neuroscience

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“…This includes the modulation of intrinsic properties and synaptic inputs to motor neurons and other populations of neurons that make up the pattern formation elements and rhythm-generating components of locomotor CPGs. Indeed, dopamine does increase the excitability of motor neurons by reducing potassium conductances (I A , SK Ca ) (Han et al 2007) and increasing excitatory glutamatergic transmission onto motor neurons (Han and Whelan 2009) that could contribute to dopamine's excitatory increase on burst amplitude. However, further work is required to probe how dopamine modulates other components of the locomotor network.…”

Section: Discussionmentioning

confidence: 99%

“…What we do know is that dopamine is released within the spinal cord during stepping activity (Gerin and Privat 1998;Jordan and Schmidt 2002) to alter motor output (Barbeau and Rossignol 1991;Clemens et al 2012;Han et al 2007;Han and Whelan 2009;Lapointe et al 2009;Madriaga et al 2004;McCrea et al 1997) and modulate sensory transmission in a variety of species. Dopaminergic fibers project from the diencephalon (A11 area), and all five dopamine receptors are present in the ventral horn of the adult mouse spinal cord (Holstege et al 1996;Qu et al 2006;Ridet et al 1992;Weil-Fugazza and Godefroy 1993;Yoshida and Tanaka 1988;Zhu et al 2007), where motor circuits are located.…”

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confidence: 99%

Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord

Sharples

Humphreys

Jensen

et al. 2015

Journal of Neurophysiology

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Sharples SA, Humphreys JM, Jensen AM, Dhoopar S, Delaloye N, Clemens S, Whelan PJ. Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord. J Neurophysiol 113: 2500 -2510, 2015. First published February 4, 2015 doi:10.1152/jn.00849.2014.-Dopamine is now well established as a modulator of locomotor rhythms in a variety of developing and adult vertebrates. However, in mice, while all five dopamine receptor subtypes are present in the spinal cord, it is unclear which receptor subtypes modulate the rhythm. Dopamine receptors can be grouped into two families-the D 1/5 receptor group and the D 2/3/4 group, which have excitatory and inhibitory effects, respectively. Our data suggest that dopamine exerts contrasting dose-dependent modulatory effects via the two receptor families. Our data show that administration of dopamine at concentrations Ͼ35 M slowed and increased the regularity of a locomotor rhythm evoked by bath application of 5-hydroxytryptamine (5-HT) and N-methyl-D(L)-aspartic acid (NMA).This effect was independent of the baseline frequency of the rhythm that was manipulated by altering the NMA concentration. We next examined the contribution of the D 1 -and D 2 -like receptor families on the rhythm. Our data suggest that the D 1 -like receptor contributes to enhancement of the stability of the rhythm. Overall, the D 2 -like family had a pronounced slowing effect on the rhythm; however, quinpirole, the D 2 -like agonist, also enhanced rhythm stability. These data indicate a receptor-dependent delegation of the modulatory effects of dopamine on the spinal locomotor pattern generator. dopamine; locomotion; monoamine; spinal cord NEURAL CIRCUITS that produce basic rhythmic motor patterns of locomotion, in vertebrates, reside primarily in the spinal cord and are subject to neuromodulation from a wide range of sources both intrinsic and extrinsic to the spinal cord (Dunbar et al.

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“…Dopamine may also facilitate motoneuron excitability indirectly by amplifying glutamatergic transmission (Han and Whelan 2009). In vitro results show that activation of D 1 -like receptors can potentiate excitatory postsynaptic glutamatergic currents on neostriatal neurons (Umemiya and Raymond 1997) and boost AMPA-evoked currents in spinal motoneurons (Yang 2000).…”

Section: Dopamine Excites Motoneurons By a D 1 -Like Receptor Mechanismmentioning

confidence: 99%

“…Dopamine release profiles in the vicinity of spinal motoneurons are correlated with changes in global motor activity (Gerin and Privat 1998). Finally, and most importantly, dopamine directly influences the excitability of spinal motoneurons in vitro (Han et al 2007;Han and Whelan 2009).…”

mentioning

confidence: 99%

Dopamine triggers skeletal muscle tone by activating D₁-like receptors on somatic motoneurons

Schwarz¹,

Peever

2011

Journal of Neurophysiology

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Schwarz PB, Peever JH. Dopamine triggers skeletal muscle tone by activating D 1 -like receptors on somatic motoneurons. J Neurophysiol 106: 1299 -1309, 2011. First published June 8, 2011 doi:10.1152/jn.00230.2011The dopamine system plays an integral role in motor physiology. Dopamine controls movement by modulation of higher-order motor centers (e.g., basal ganglia) but may also regulate movement by directly controlling motoneuron function. Even though dopamine cells synapse onto motoneurons, which themselves express dopamine receptors, it is unknown whether dopamine modulates skeletal muscle activity. Therefore, we aimed to determine whether changes in dopaminergic neurotransmission at a somatic motor pool affect motor outflow to skeletal muscles. We used microinjection, neuropharmacology, electrophysiology, and histology to determine whether manipulation of D 1 -and D 2 -like receptors on trigeminal motoneurons affects masseter and/or tensor palatini muscle tone in anesthetized rats. We found that apomorphine (a dopamine analog) activated trigeminal motoneurons and triggered a potent increase in both masseter and tensor palatini tone. This excitatory effect is mediated by D 1 -like receptors because specific D 1 -like receptor activation strengthened muscle tone and blockade of these receptors prevented dopamine-driven activation of motoneurons. Blockade of D 1 -like receptors alone had no detectable effect on basal masseter/tensor palatini tone, indicating the absence of a functional dopamine drive onto trigeminal motoneurons, at least during isoflurane anesthesia. Finally, we showed that D 2 -like receptors do not affect either trigeminal motoneuron function or masseter/tensor palatini muscle tone. Our results provide the first demonstration that dopamine can directly control movement by manipulating somatic motoneuron behavior and skeletal muscle tone.

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Modulation of AMPA currents by D1-like but not D2-like receptors in spinal motoneurons

Cited by 38 publications

References 46 publications

Dopamine Acts as a Partial Agonist for 2A Adrenoceptor in Melanin-Concentrating Hormone Neurons

Dopamine Acts as a Partial Agonist for 2A Adrenoceptor in Melanin-Concentrating Hormone Neurons

Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord

Dopamine triggers skeletal muscle tone by activating D₁-like receptors on somatic motoneurons

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Modulation of AMPA currents by D1-like but not D2-like receptors in spinal motoneurons

Cited by 38 publications

References 46 publications

Dopamine Acts as a Partial Agonist for 2A Adrenoceptor in Melanin-Concentrating Hormone Neurons

Dopamine Acts as a Partial Agonist for 2A Adrenoceptor in Melanin-Concentrating Hormone Neurons

Dopaminergic modulation of locomotor network activity in the neonatal mouse spinal cord

Dopamine triggers skeletal muscle tone by activating D1-like receptors on somatic motoneurons

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Dopamine triggers skeletal muscle tone by activating D₁-like receptors on somatic motoneurons