Receptor and Ionic Mechanism of Histamine on Mouse Dorsolateral Striatal Neurons

Peng, Jian-Ya; Shen, Kang-Li; Fan, Xiu-Juan; Qi, Zengxin; Huang, Hua; Jiang, Jian-Lan; Lu, Jian-Hua; Wang, Xiaoqin; Fang, Xiao-Xia; Yuan, Wang-Rui; Deng, Qiao-Xuan; Chen, Shu; Chen, Liang; Zhuang, Qian-Xing

doi:10.1007/s12035-022-03076-y

Cited by 6 publications

(11 citation statements)

References 58 publications

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“…Further, the histaminergic projections from the TMN have been shown to make a generalised neural activation to the maintenance of arousal (Moruzzi and Magoun 1949 ; Olson and Fuxe 1971 ; Panula et al 1991 ). It has recently been revealed that the central acting components of histamine have motor cortical projections (Peng et al 2023 ), thus, the central motor response cannot fully be reduced to mAChRs from the current study. Another potential explanation for this result includes the ceiling effect that the pain from the neuromuscular fatigue may have upon the MEP and motor output.…”

Section: Discussioncontrasting

confidence: 53%

Muscarinic acetylcholine activity modulates cortical silent period, but not motor evoked potentials, during muscle contractions

Dempsey¹,

Kavanagh²

2023

Exp Brain Res

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This study used transcranial magnetic stimulation (TMS) to determine if muscarinic receptor blockade affects muscle responses during voluntary contractions. Motor evoked potentials (MEPs) were recorded from biceps brachii in 10 subjects (age: 23 ± 2) during 10%, 25%, 50%, 75%, and 100% maximal voluntary contractions (MVCs). Each contraction intensity was examined under non-fatigued and fatigued conditions. All measurements were obtained post-ingestion of 25 mg promethazine or placebo. MEP area and the duration of the TMS-evoked silent period (SP) were calculated for all contractions. No drug-related differences were detected for MEP area during non-fatigued or fatigued contractions. A main effect of drug was detected for the SP (p = 0.019) where promethazine increased SP duration by an average of 0.023 $$\pm$$ ± 0.015 s. This drug effect was only identified for the unfatigued contractions and not following the sustained fatiguing contractions (p = 0.105). The cholinergic system does not influence corticospinal excitability during voluntary muscle contractions, but instead affects neural circuits associated with the TMS-evoked SP. Given the prevalence of cholinergic properties in prescription and over-the-counter medications, the current study enhances our understanding of mechanisms that may contribute to motor side-effects.

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Section: Discussioncontrasting

confidence: 53%

Muscarinic acetylcholine activity modulates cortical silent period, but not motor evoked potentials, during muscle contractions

Dempsey¹,

Kavanagh²

2023

Exp Brain Res

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“…We first determined the ionic mechanism downstream of H 2 R. Previous studies have shown that H 2 R elicites I h through the coupled HCN channel ( 25 , 29 , 30 ). To elucidate the ionic mechanisms underlying H 2 R-induced excitability of EPN PV neurons, we performed whole-cell patch-clamp recordings on labeled EPN PV neurons in vitro ( SI Appendix , Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, the concentrations of histaminergic drugs that we used in the long-term microinfiltrated release in vivo may be close to those that acted on EPN PV neurons. The range of concentrations of histaminergic drugs administered in previous studies has varied widely, which may be due to the differences in the area of the brain affected by histaminergic drugs or in the way they are administered ( 28 , 29 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that histamine is involved in the regulation of various functions such as the sleep–wake cycle, energy and endocrine homeostasis, synaptic plasticity, and learning via its receptors ( 23 , 25 – 27 ). Recent studies have shown that histamine is involved in motor control by affecting basal ganglia nuclei such as the lateral globus pallidus (LGP), striatum, and STN ( 28 – 30 ). Studies on postmortem PD patients have also shown the involvement of histamine in the pathological process of PD, and a significant increase in the histamine concentration was detected in most basal ganglia nuclei, including the putamen, SNc, and globus pallidus, in the brain samples of PD patients ( 24 , 31 , 32 ).…”

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confidence: 99%

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Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus–thalamus circuitry

Peng

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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In Parkinson’s disease (PD), reduced dopamine levels in the basal ganglia have been associated with altered neuronal firing and motor dysfunction. It remains unclear whether the altered firing rate or pattern of basal ganglia neurons leads to parkinsonism-associated motor dysfunction. In the present study, we show that increased histaminergic innervation of the entopeduncular nucleus (EPN) in the mouse model of PD leads to activation of EPN parvalbumin (PV) neurons projecting to the thalamic motor nucleus via hyperpolarization-activated cyclic nucleotide–gated (HCN) channels coupled to postsynaptic H 2 R. Simultaneously, this effect is negatively regulated by presynaptic H 3 R activation in subthalamic nucleus (STN) glutamatergic neurons projecting to the EPN. Notably, the activation of both types of receptors ameliorates parkinsonism-associated motor dysfunction. Pharmacological activation of H 2 R or genetic upregulation of HCN2 in EPN PV neurons, which reduce neuronal burst firing, ameliorates parkinsonism-associated motor dysfunction independent of changes in the neuronal firing rate. In addition, optogenetic inhibition of EPN PV neurons and pharmacological activation or genetic upregulation of H 3 R in EPN-projecting STN Glu neurons ameliorate parkinsonism-associated motor dysfunction by reducing the firing rate rather than altering the firing pattern of EPN PV neurons. Thus, although a reduced firing rate and more regular firing pattern of EPN PV neurons correlate with amelioration in parkinsonism-associated motor dysfunction, the firing pattern appears to be more critical in this context. These results also confirm that targeting H 2 R and its downstream HCN2 channel in EPN PV neurons and H 3 R in EPN-projecting STN Glu neurons may represent potential therapeutic strategies for the clinical treatment of parkinsonism-associated motor dysfunction.

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“…Otherwise, all outliers were included in the statistical analysis. Group size selection for each protocol or study was determined based on previous studies (Peng et al, 2023; Zhuang, Li, et al, 2018). The group size (n) represents independent values described in the figure legend, such as the number of individual animals or the number of neurons/sections typically derived from n = 9 mice, and statistical analysis was performed using these independent values.…”

Section: Methodsmentioning

confidence: 99%

Histamine bidirectionally regulates the intrinsic excitability of parvalbumin‐positive neurons in the lateral globus pallidus and promotes motor behaviour

Shen

Peng

et al. 2023

British J Pharmacology

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Background and Purpose Parvalbumin (PV)‐positive neurons are a type of neuron in the lateral globus pallidus (LGP) which plays an important role in motor control. The present study investigated the effect of histamine on LGPPV neurons and motor behaviour. Experimental Approach Histamine levels in LGP as well as its histaminergic innervation were determined through brain stimulation, microdialysis, anterograde tracing and immunostaining. Mechanisms of histamine action were detected by immunostaining, single‐cell qPCR, whole‐cell patch‐clamp recording, optogenetic stimulation and CRISPR/Cas9 gene‐editing techniques. The effect of histamine on motor behaviour was detected by animal behavioural tests. Key Results A direct histaminergic innervation in LGP from the tuberomammillary nucleus (TMN) and a histamine‐induced increase in the intrinsic excitability of LGPPV neurons were determined by pharmacological blockade or by genetic knockout of the histamine H1 receptor (H1R)‐coupled TWIK‐related potassium channel‐1 (TREK‐1) and the small‐conductance calcium‐activated potassium channel (SK3), as well as by activation or overexpression of the histamine H2 receptor (H2R)‐coupled hyperpolarization‐activated cyclic nucleotide‐gated channel (HCN2). Histamine negatively regulated the STN → LGPGlu transmission in LGPPV neurons via the histamine H3 receptor (H3R), whereas blockage or knockout of H3R increased the intrinsic excitability of LGPPV neurons. Conclusions and Implications Our results indicated that the endogenous histaminergic innervation in the LGP can bidirectionally promote motor control by increasing the intrinsic excitability of LGPPV neurons through postsynaptic H1R and H2R, albeit its action was negatively regulated by the presynaptic H3R, thereby suggesting possible role of histamine in motor deficits manifested in Parkinson's disease (PD).

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Receptor and Ionic Mechanism of Histamine on Mouse Dorsolateral Striatal Neurons

Cited by 6 publications

References 58 publications

Muscarinic acetylcholine activity modulates cortical silent period, but not motor evoked potentials, during muscle contractions

Muscarinic acetylcholine activity modulates cortical silent period, but not motor evoked potentials, during muscle contractions

Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus–thalamus circuitry

Histamine bidirectionally regulates the intrinsic excitability of parvalbumin‐positive neurons in the lateral globus pallidus and promotes motor behaviour

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