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The Journal of Neuroscience, August 1, 1999, 19(15):6475-6487

Ultrastructural Localization of the 4-Subunit of the Neuronal Acetylcholine Nicotinic Receptor in the Rat Substantia Nigra

Maria del Mar Arroyo-Jiménez^{1, 2, 3}, Jean-Pierre Bourgeois¹, Lisa M. Marubio¹, Anne-Marie Le Sourd¹, Ole Petter Ottersen⁴, Eric Rinvik⁴, Alfonso Fairén^{2, 3}, and Jean-Pierre Changeux¹

¹ Neurobiologie Moléculaire, Unité Associée Centre National de la Recherche Scientifique D1284, Département des Biotechnologies, Institut Pasteur, 75724 Paris Cedex 15, France, ² Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain, ³ Instituto de Neurociencias, Universidad Miguel Hernández, 03550 San Juan de Alicante, Spain, and ⁴ Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Blindern N-0317, Oslo, Norway

The distribution of the 4-subunit of the neuronal nicotinic acetylcholine receptor (nAChR) in the rat brain was examined at light and electron microscopy levels using immunohistochemical staining. In the present study we demonstrate the specificity, in both tissue homogenates and brain sections, of a polyclonal antibody raised against the rat nAChR 4-subunit. The characterization of this antibody involved: (1) Western blot analysis of rat brain homogenates and membrane extracts from cells previously transfected with diverse combinations of neuronal nAChR subunits, and (2) immunohistochemistry using transfected cells and rat brain tissue.

At the light microscope level, the 4-subunit-like-immunoreactivity (LI) was widely distributed in the rat brain and matched the distribution of the 4-subunit transcripts observed previously by in situ hybridization. Strong immunohistochemical labeling was detected in the mesencephalic dopaminergic nuclei. The nAChRs in this region are thought to be responsible for the modulation of dopaminergic transmission. The neurotransmitter identity of 4-immunolabeled neurons in the substantia nigra pars compacta (SNpc) and the ventral tegmental area was thus assessed by investigating the possible colocalization of the nAChR 4-subunit with tyrosine hydroxylase using confocal microscopy. The double labeling experiments unambiguously indicated that the 4-subunit-LI is present in dopaminergic neurons.

At the electron microscope level, the neurons in the SNpc exhibited 4-subunit-LI in association with a minority of postsynaptic densities, suggesting that the 4-subunit may be a component of functional nAChRs mediating synaptic transmission between midbrain cholinergic neurons and mesencephalic dopaminergic neurons.

Key words: neuronal nAChR; immunohistochemistry; immunogold; postsynaptic localization; substantia nigra; dopaminergic nuclei; rat brain

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19156475-13$05.00/0

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