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Imidazoleacetic acid-ribotide in vestibulo-sympathetic pathway neurons

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Abstract

Imidazole-4-acetic acid-ribotide (IAARP) is a putative neurotransmitter/modulator and an endogenous regulator of sympathetic drive, notably systemic blood pressure, through binding to imidazoline receptors. IAARP is present in neurons and processes throughout the CNS, but is particularly prevalent in regions that are involved in blood pressure control. The goal of this study was to determine whether IAARP is present in neurons in the caudal vestibular nuclei that participate in the vestibulo-sympathetic reflex (VSR) pathway. This pathway is important in modulating blood pressure upon changes in head position with regard to gravity, as occurs when humans rise from a supine position and when quadrupeds climb or rear. Sinusoidal galvanic vestibular stimulation was used to activate the VSR and cfos gene expression in VSR pathway neurons of rats. These subjects had previously received a unilateral FluoroGold tracer injection in the rostral or caudal ventrolateral medullary region. The tracer was transported retrogradely and filled vestibular neuronal somata with direct projections to the injected region. Brainstem sections through the caudal vestibular nuclei were immunostained to visualize FluoroGold, cFos protein, IAARP and glutamate immunofluorescence. The results demonstrate that IAARP is present in vestibular neurons of the VSR pathway, where it often co-localizes with intense glutamate immunofluorescence. The co-localization of IAARP and intense glutamate immunofluorescence in VSR neurons may represent an efficient chemoanatomical configuration, allowing the vestibular system to rapidly up- and down-modulate the activity of presympathetic neurons in the ventrolateral medulla, thereby altering blood pressure.

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Acknowledgments

The authors are grateful to Dr. Sergei Yakushin for assistance with the sGVS stimulation, Dr. Ewa Kukielka for technical assistance, and Dr. George Prell for helpful discussions concerning IAARP. The research was supported by NIH Grant DC008846.

Author contributions

All authors approved the final version of this article. Experiments were conceived and designed by GH, GM, and VF. GM performed the tracer injections, sGVS stimulation, and immunolabeling studies; GH performed the microscopy, image processing, and data analysis. GH prepared the figures, and all authors contributed to the manuscript preparation.

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Authors and Affiliations

  1. Department of Neurology, Icahn School of Medicine at Mount Sinai, Box 1140, One Gustave L. Levy Place, New York, NY, 10029, USA

    Gay R. Holstein & Giorgio P. Martinelli

  2. Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Gay R. Holstein & Victor L. Friedrich Jr.

  3. Department of Anatomy/Functional Morphology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Gay R. Holstein

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  1. Gay R. Holstein
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  2. Victor L. Friedrich Jr.
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Correspondence to Gay R. Holstein.

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Holstein, G.R., Friedrich, V.L. & Martinelli, G.P. Imidazoleacetic acid-ribotide in vestibulo-sympathetic pathway neurons. Exp Brain Res 234, 2747–2760 (2016). https://doi.org/10.1007/s00221-016-4725-2

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