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Laminar distribution of neurotransmitter receptors in different reeler mouse brain regions

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Abstract

Mapping of multiple receptors of neurotransmitters provides insight into the spatial distribution of neurotransmission-relevant molecules in the cerebral cortex. During development, lack of reelin leads to impaired migration, disturbed lamination of the hippocampus and inverted neocortical layering. In the adult, reelin may regulate synaptic plasticity by modulating neurotransmitter receptor function. Using quantitative in vitro receptor autoradiography, different receptors, in particular, the binding site densities and laminar distribution of various glutamate, GABA, muscarinic and nicotinic acetylcholine, serotonin, dopamine and adenosine receptors, were analyzed in cortical and subcortical structures of reeler and wild-type brains. Differential changes in the laminar distribution, maximum binding capacity (B max) and regional density of neurotransmitter receptors were found in the reeler brain. A decrease of whole brain B max was found for adenosine A1 and GABAA receptors. In the forebrain, several binding sites were differentially up- or down-regulated (kainate, A1, benzodiazepine, 5-HT1, M2, α1 and α2). In the hippocampus, a significant decrease of GABAB, 5-HT1 and \( {\text{A}}_1^{\prime} \) receptors were observed. The density of M2 receptors increased, while other receptors remained unchanged. In the neocortex, some receptors demonstrated an obviously inverted laminar distribution (AMPA, kainate, NMDA, GABAB, 5-HT1, M1, M3, nAch), while the distribution of others (A1, GABAA, benzodiazepine, 5-HT2, muscarinic M2, adrenergic α1, α2) seemed to be less affected. Thus, the laminar receptor distribution is modulated by the developmental impairment and suggests and reflects partially the laminar inversion in reeler mice.

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Acknowledgments

The excellent technical assistance by S. Buller, M. Cremer and S. Wilms is very much appreciated. We further thank Dr. Axel Schleicher for helpful comments on the data, and Drs. Iris Hack and Astrid Rollenhagen for their critical reading and comments on the final version of the manuscript. This work was supported by the Initiative and Networking Fund of the Helmholtz Association (Helmholtz Alliance on Mental Health in an Ageing Society).

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Authors and Affiliations

  1. Institute of Neuroscience and Medicine INM-2, Research Centre Jülich GmbH, 52425, Jülich, Germany

    Christian M. Cremer, Joachim H. R. Lübke, Nicola Palomero-Gallagher & Karl Zilles

  2. C. & O. Vogt Institute for Brain Research, Heinrich-Heine-University Düsseldorf, 40225, Düsseldorf, Germany

    Christian M. Cremer & Karl Zilles

  3. JARA Translational Brain Medicine, Jülich, Aachen, Germany

    Joachim H. R. Lübke & Karl Zilles

  4. Department of Psychiatry and Psychotherapy, Medical Faculty, RWTH/University Hospital Aachen, 52074, Aachen, Germany

    Joachim H. R. Lübke

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  1. Christian M. Cremer
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Correspondence to Joachim H. R. Lübke.

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The authors C. M. Cremer and J. H. R. Lübke have equally contributed to the work.

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Supplementary Fig. 1: Distribution of adrenergic α1 and α2 receptor subtypes in wild-type and reeler mice. Color-coded autoradiographs of a representative section of a wild-type (left) and reeler mouse (right) hemisphere showing the distribution of α1 (A, A1) and α2 (B, B1) receptors. A2, B2 Laminar distribution of α1 (upper right panel) and α2 (lower right panel) receptors in the primary somatosensory cortex of wild-type and the reeler mutant mice.

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Cremer, C.M., Lübke, J.H.R., Palomero-Gallagher, N. et al. Laminar distribution of neurotransmitter receptors in different reeler mouse brain regions. Brain Struct Funct 216, 201–218 (2011). https://doi.org/10.1007/s00429-011-0303-3

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