Substance P excites globus pallidus neurons <i>in vivo</i>

Cui, Qiaoling; Yung, Wing‐Ho; Xue, Yan; Chen, Lei

doi:10.1111/j.1460-9568.2007.05803.x

Cited by 12 publications

(6 citation statements)

References 63 publications

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“…The dose-response relationship of the effect of SM-SP is bell-shaped, with a maximum response observed at 0.3 and 1 μM of the agonist. Interestingly, such a bell-shaped dose-response relationship has also been found in our previous in vivo study (Cui et al, 2007) and other studies (e.g. Khan et al, 1996; de Araujo et al, 1998).…”

Section: Discussionsupporting

confidence: 85%

“…The present study showed that pretreatment with a selective neurokinin-1 receptor antagonist, SR140333B, can block SM-SP-induced depolarization. Our previous in vivo extracellular recordings showed that SR140333B decreased the spontaneous firing rate in some pallidal neurons, indicating an involvement of endogenous substance P system in modulating electrical activity of pallidal neurons (Cui et al, 2007). However, the data reported here revealed that, under the present in vitro condition, neurokinin-1 receptor antagonist had no effect on the membrane properties, suggesting that there was no tonic action of neurokinin-1 receptor on pallidal neurons.…”

Section: Discussionmentioning

confidence: 96%

“…Therefore, to fully understand the role of substance P in basal ganglia under normal and pathological conditions, it is important to determine the actions of substance P in the globus pallidus. Recently, our previous in vivo extracellular recording and behavioral experiments revealed that substance P can excite globus pallidus neuron (Cui et al, 2007). To further identify the cellular mechanisms of substance P-induced excitation in globus pallidus, whole-cell patch-clamp recording was employed in the present experiment to address this question.…”

Section: Introductionmentioning

confidence: 99%

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Neurokinin-1 receptor activation in globus pallidus

2009

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The undecapeptide substance P has been demonstrated to modulate neuronal activity in a number of brain regions by acting on neurokinin-1 receptors. Anatomical studies revealed a moderate level of neurokinin-1 receptor in rat globus pallidus. To determine the electrophysiological effects of neurokinin-1 receptor activation in globus pallidus, whole-cell patch-clamp recordings were performed in the present study. Under current-clamp recordings, neurokinin-1 receptor agonist, [Sar9, Met(O2)11] substance P (SM-SP) at 1 μM, depolarized globus pallidus neurons and increased their firing rate. Consistently, SM-SP induced an inward current under voltage-clamp recording. The depolarization evoked by SM-SP persisted in the presence of tetrodotoxin, glutamate and GABA receptor antagonists, indicating its direct postsynaptic effects. The neurokinin-1 receptor antagonist, SR140333B, could block SM-SP-induced depolarization. Further experiments showed that suppression of potassium conductance was the predominant ionic mechanism of SM-SP-induced depolarization. To determine if neurokinin-1 receptor activation exerts any effects on GABAergic and glutamatergic neurotransmission, the action of SM-SP on synaptic currents was studied. SM-SP significantly increased the frequency of spontaneous inhibitory postsynaptic currents, but only induced a transient increase in the frequency of miniature inhibitory postsynaptic currents. No change was observed in both spontaneous and miniature excitatory postsynaptic currents. Based on the direct excitatory effects of SM-SP on pallidal neurons, we hypothesize that neurokinin-1 receptor activation in globus pallidus may be involved in the beneficial effect of substance P in Parkinson's disease.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Neurokinin-1 receptor activation in globus pallidus

2009

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“…The major finding of this study is that the neuropeptide SP excites relay neurons in the LPl nucleus, which could significantly influence the transfer of visual information from primary visual cortex to higher visual cortices, as well as influence the integration of afferent inputs arising from SC. While there have been electrophysiological studies of the functional role of SP in other regions of the brain such as the striatum, hippocampus, globus pallidus, locus coeruleus (Shen & North, 1992; Cui et al. , 2007; Suwabe & Bradley, 2007; Blomeley & Bracci, 2008; Ogier et al.…”

Section: Discussionmentioning

confidence: 99%

“…SP has been found to alter neuronal function in various brain regions, including the striatum, hippocampus, globus pallidus and locus coeruleus (Shen & North, 1992; Cui et al. , 2007; Suwabe & Bradley, 2007; Blomeley & Bracci, 2008; Ogier et al.…”

Section: Introductionmentioning

confidence: 99%

Excitatory actions of substance P in the rat lateral posterior nucleus

Paul

Cox

2009

Eur J of Neuroscience

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The lateral posterior nucleus (LP) receives inputs from both neocortex and superior colliculus (SC), and is involved with integration and processing of higher-level visual information. Relay neurons in LP contain tachykinin receptors and are innervated by substance P (SP)-containing SC neurons and by layer V neurons of the visual cortex. In this study, we investigated the actions of SP on LP relay neurons using whole-cell recording techniques. SP produced a graded depolarizing response in LP neurons along the rostro-caudal extent of the lateral subdivision of LP nuclei (LPl), with a significantly larger response in rostral LPl neurons compared with caudal LPl neurons. In rostral LPl, SP (5-2000 nm) depolarized nearly all relay neurons tested (> 98%) in a concentration-dependent manner. Voltage-clamp experiments revealed that SP produced an inward current associated with a decreased conductance. The inward current was mediated primarily by neurokinin receptor (NK)(1) tachykinin receptors, although significantly smaller inward currents were produced by specific NK2 and NK3 receptor agonists. The selective NK(1) receptor antagonist RP67580 attenuated the SP-mediated response by 71.5% and was significantly larger than the attenuation of the SP response obtained by NK2 and NK3 receptor antagonists, GR159897 and SB222200, respectively. The SP-mediated response showed voltage characteristics consistent with a K+ conductance, and was attenuated by Cs+, a K+ channel blocker. Our data suggest that SP may modulate visual information that is being processed and integrated in the LPl with inputs from collicular sources.

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Substance P effects exclusively on prototypic neurons in mouse globus pallidus

et al. 2017

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Previous studies have suggested that the neurokinin-1 receptor (NK-1R) expressing neurons in the globus pallidus (GP) receive substance P (SP), presumably released by axon collaterals of striatal direct neurons. However, the effect of SP on the GP remains unclear. In this study, we identified that the SP-responsive cells comprise a highly specific cell type in the GP with regard to immunofluorescence, electrophysiology, and projection properties. Morphologically, NK-1R-immunoreactive neurons occasionally co-expressed parvalbumin (PV) and/or Lim-homeobox 6 (Lhx6), but not Forkhead box protein P2 (FoxP2), which is mainly expressed by arkypallidal neurons. Retrograde tracing experiments also showed that some of GP neurons projecting to the subthalamic nucleus (namely prototypic neurons) expressed NK-1R as well as Lhx6 and/or PV, but not FoxP2. In vitro electrophysiological study revealed that, among 48 GP neurons, the SP agonist induced inward current in 21 neurons. The response was prevented by bath application of the NK-1R antagonist. Based on the firing properties, 92 recorded GP neurons were classified into three distinct types, i.e., CL1, 2, and 3. Interestingly, all the SP-responsive neurons were found to be in CL2 and CL3 types, but not in CL1. Moreover, active and passive membrane properties of the neurons in those clusters and immunofluorescent identification suggested that CL1 and CL2/3 could be considered as arkypallidal and prototypic neurons, respectively. Therefore, SP-responsive neurons were one of the populations of prototypic neurons based on both anatomical and electrophysiological results. Altogether, the striatal direct pathway neurons could affect the indirect pathway in the way of prototypic neurons, via the action of SP to NK-1R.

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Substance P excites globus pallidus neurons in vivo

Cited by 12 publications

References 63 publications

Neurokinin-1 receptor activation in globus pallidus

Neurokinin-1 receptor activation in globus pallidus

Excitatory actions of substance P in the rat lateral posterior nucleus

Substance P effects exclusively on prototypic neurons in mouse globus pallidus

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