Institute of Neuroscience and Medicine INM-2, Research Centre Jülich GmbH, 52425 Jülich, Germany.
Brain Struct Funct. 2011 Sep;216(3):201-18. doi: 10.1007/s00429-011-0303-3. Epub 2011 Mar 27.
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.
多种神经递质受体的定位提供了对大脑皮层中与神经传递相关分子的空间分布的深入了解。在发育过程中,缺乏 reelin 会导致海马体迁移受损、层状结构紊乱和新皮层层状结构反转。在成年期,reelin 可能通过调节神经递质受体功能来调节突触可塑性。使用定量的体外受体放射自显影技术,分析了 reeler 和野生型大脑皮质和皮质下结构中不同的受体,特别是各种谷氨酸、GABA、毒蕈碱和烟碱型乙酰胆碱、5-羟色胺、多巴胺和腺苷受体的结合位点密度和层状分布。在 reeler 大脑中发现了神经递质受体的层状分布、最大结合容量(B(max))和区域密度的差异变化。全脑 B(max)发现腺苷 A(1)和 GABA(A)受体减少。在前脑,几个结合位点的表达上调或下调(红藻氨酸、A(1)、苯二氮䓬、5-HT(1)、M(2)、α(1)和α(2))。在海马体中,GABA(B)、5-HT(1)和 A'₁受体显著减少。M(2)受体密度增加,而其他受体保持不变。在新皮层中,一些受体表现出明显的层状反转分布(AMPA、红藻氨酸、NMDA、GABA(B)、5-HT(1)、M(1)、M(3)、nAch),而其他受体(A(1)、GABA(A)、苯二氮䓬、5-HT(2)、毒蕈碱 M(2)、肾上腺素能 α(1)、α(2))的分布似乎受影响较小。因此,层状受体分布受发育障碍的调节,并部分反映了 reeler 小鼠的层状反转。