Resumen de Laminar distribution of neurotransmitter receptors in different reeler mouse brain regions.

Christian M Cremer, Joachim Lübke, Nicola Palomero-Gallagher, Karl Zilles

• 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 A(1) and GABA(A) receptors. In the forebrain, several binding sites were differentially up- or down-regulated (kainate, A(1), benzodiazepine, 5-HT(1), M(2), α(1) and α(2)). In the hippocampus, a significant decrease of GABA(B), 5-HT(1) and A'₁ receptors were observed. The density of M(2) receptors increased, while other receptors remained unchanged. In the neocortex, some receptors demonstrated an obviously inverted laminar distribution (AMPA, kainate, NMDA, GABA(B), 5-HT(1), M(1), M(3), nAch), while the distribution of others (A(1), GABA(A), benzodiazepine, 5-HT(2), muscarinic M(2), adrenergic α(1), α(2)) 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.;