Histamine promotes rat motor performances by activation of H2 receptors in the cerebellar fastigial nucleus

et al. 2015

Mol Neurobiol

Self Cite

Insights into function of central histaminergic system, a general modulator originating from the hypothalamus for whole brain activity, in motor control are critical for understanding the mechanism underlying somatic-nonsomatic integration. Here, we show a novel selective role of histamine in the cerebellar nuclei, the final integrative center and output of the cerebellum. Histamine depolarizes projection neurons but not interneurons in the cerebellar nuclei via the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to histamine H2 receptors, which are exclusively expressed on glutamatergic and glycinergic projection neurons. Furthermore, blockage of HCN channels to block endogenous histaminergic afferent inputs in the cerebellar nuclei significantly attenuates motor balance and coordination. Therefore, through directly and quickly modulation on projection neurons but not interneurons in the cerebellar nuclei, central histaminergic system may act as a critical biasing force to not only promptly regulate ongoing movement but also realize a rapid integration of somatic and nonsomatic response.

Section: Introductionmentioning

confidence: 99%

Selective Modulation of Histaminergic Inputs on Projection Neurons of Cerebellum Rapidly Promotes Motor Coordination via HCN Channels

Zhang

et al. 2015

Mol Neurobiol

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“…Besides the vestibular nuclear complex in the brainstem, various important subcortical motor structures have been found to receive and be modulated by direct hypothalamic histaminergic projections, including the cerebellum [23,26], the red nucleus [24], the substantia nigra [40,41], the neostriatum [42] and the globus pallidus [25] in the basal ganglia. Interestingly, without exception, neurons in all these subcortical motor centers are uniformly excited by histamine.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, the central histaminergic system may ultimately regulate movements. In fact, in the cerebellum, histamine/the histaminergic afferents regulate the cerebellar nuclear neuronal activity and improve motor balance and motor coordination during ongoing movements [26,44]. Also, depletion of brain histamine or knockout of histamine receptors alters ambulatory activity and reduces exploratory behavior [45,46,47].…”

Section: Discussionmentioning

confidence: 99%

“…In some experiments, low-Ca 2+ /high-Mg 2+ medium was used to decrease presynaptic neurotransmitter release. In these cases, the concentration of Ca 2+ was lowered to 0.3 m M and Mg 2+ was raised to 9.0 m M [23,24,25,26,27]. Histamine or histamine receptor agonist was added to the perfusing ACSF to stimulate the recorded SVN neuron for a test period of 1 min.…”

Section: Methodsmentioning

confidence: 99%

“…Rob Leurs (VU University Amsterdam, Amsterdam, The Netherlands). The concentrations of histaminergic reagents were chosen according to previous reports [4,6,23,24,25,26,27,29,30]. …”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Histamine Excites Rat Superior Vestibular Nuclear Neurons via Postsynaptic H₁and H₂Receptors in vitro

et al. 2013

Neurosignals

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The superior vestibular nucleus (SVN), which holds a key position in vestibulo-ocular reflexes and nystagmus, receives direct hypothalamic histaminergic innervations. By using rat brainstem slice preparations and extracellular unitary recordings, we investigated the effect of histamine on SVN neurons and the underlying receptor mechanisms. Bath application of histamine evoked an excitatory response of the SVN neurons, which was not blocked by the low-Ca²⁺/high-Mg²⁺ medium, indicating a direct postsynaptic effect of the amine. Selective histamine H₁ receptor agonist 2-pyridylethylamine and H₂ receptor agonist dimaprit, rather than VUF8430, a selective H₄ receptor agonist, mimicked the excitation of histamine on SVN neurons. In addition, selective H₁ receptor antagonist mepyramine and H₂ receptor antagonist ranitidine, but not JNJ7777120, a selective H₄ receptor antagonist, partially blocked the excitatory response of SVN neurons to histamine. Moreover, mepyramine together with ranitidine nearly totally blocked the histamine-induced excitation. Immunostainings further showed that histamine H₁ and H₂ instead of H₄ receptors existed in the SVN. These results demonstrate that histamine excites the SVN neurons via postsynaptic histamine H₁ and H₂ receptors, and suggest that the central histaminergic innervation from the hypothalamus may actively bias the SVN neuronal activity and subsequently modulate the SVN-mediated vestibular functions and gaze control.

5-HT2A receptor-mediated excitation on cerebellar fastigial nucleus neurons and promotion of motor behaviors in rats

Zhang

Pflugers Arch - Eur J Physiol

et al. 2013

It has long been known that serotonergic afferent inputs are the third largest afferent population in the cerebellum after mossy fibers and climbing fibers. However, the role of serotonergic inputs in cerebellar-mediated motor behaviors is still largely unknown. Here, we show that only 5-HT2A receptors among the 5-HT2 receptor subfamily are expressed and localized in the rat cerebellar fastigial nucleus (FN), one of the ultimate outputs of the spinocerebellum precisely regulating trunk and limb movements. Remarkably, selective activation of 5-HT2A receptors evokes a postsynaptic excitatory effect on FN neurons in a concentration-dependent manner in vitro, which is in accord with the 5-HT-elicited excitation on the same tested neurons. Furthermore, selective 5-HT2A receptor antagonist M100907 concentration-dependently blocks the excitatory effects of 5-HT and TCB-2, a 5-HT2A receptor agonist, on FN neurons. Consequently, microinjection of 5-HT into bilateral FNs significantly promotes rat motor performances on accelerating rota-rod and balance beam and narrows stride width rather than stride length in locomotion gait. All these motor behavioral effects are highly consistent with those of selective activation of 5-HT2A receptors in FNs, and blockage of the component of 5-HT2A receptor-mediated endogenous serotonergic inputs in FNs markedly attenuates these motor performances. All these results demonstrate that postsynaptic 5-HT2A receptors greatly contribute to the 5-HT-mediated excitatory effect on cerebellar FN neurons and promotion of the FN-related motor behaviors, suggesting that serotonergic afferent inputs may actively participate in cerebellar motor control through their direct modulation on the final output of the spinocerebellum.