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Alpha-adrenergic receptor (α2A ) is colocalized in basal forebrain cholinergic neurons: A light and electron microscopic double immunolabeling study

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Journal of Neurocytology

Abstract

A variety of data suggest that noradrenaline and acetylcholine may interact in the basal forebrain, however no morphological studies have addressed whether indeed cholinergic neurons express adrenergic receptors. We have investigated the presence of alpha-adrenergic receptor subtype α2A -AR in cholinergic neurons of the basal forebrain. Cholinergic neurons were identified with an antibody against choline acetyltransferase and the receptor with a polyclonal antibody raised against a 47 amino acid fragment of the third intracellular loop of the α2A -AR. For double labeling at the light microscopic level the Ni-DAB/DAB technique was used, and for electron microscopy an immunoperoxidase/immunogold method was applied. We detected the α2A -AR protein in cholinergic as well as in non-cholinergic neurons. Almost half of all cholinergic neurons contained this adrenergic receptor. Double-labeled neurons were distributed throughout the rostro-caudal extent of the basal forebrain cholinergic continuum, including the medial septum, vertical and horizontal diagonal band nuclei, pallidal regions, substantia innominata and the internal capsule. Non-cholinergic neurons that expressed the α2A -AR outnumbered cholinergic/α2A -AR neurons by several factors. Electron microscopy confirmed the presence of α2A -AR in cholinergic neurons in the medial septum, vertical and horizontal diagonal band nuclei. Gold particles (10 nm) indicative of α2A -AR were diffusely distributed in the cytoplasm and accumulated in cytoplasmic areas near the Golgi complex and cysterns of the endoplasmic reticulum and were associated with the cellular membranes at synaptic and non-synaptic locations. Since many of the α2A -AR+/non-cholinergic neurons we detected are likely to be GABAergic cells, our data support the hypothesis that noradrenaline may act via basal forebrain cholinergic and non-cholinergic neurons to influence cortical activity.

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Authors and Affiliations

  1. Rutgers University, Center for Molecular and Behavioral Neuroscience, Newark, NJ, 07102, USA

    L. Zaborszky

  2. Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, VA, 22908, USA

    D. L. Rosin

  3. Hungarian Academy of Sciences and Semmelweis University, Neuroendocrine Research Laboratory, Budapest, Hungary

    J. Kiss

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  1. L. Zaborszky
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  2. D. L. Rosin
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  3. J. Kiss
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Zaborszky, L., Rosin, D.L. & Kiss, J. Alpha-adrenergic receptor (α2A ) is colocalized in basal forebrain cholinergic neurons: A light and electron microscopic double immunolabeling study. J Neurocytol 33, 265–276 (2004). https://doi.org/10.1023/B:NEUR.0000044188.67442.9d

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