Freeman Whitney, Morton A Jennifer
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Brain Res Bull. 2004 Mar 1;63(1):33-44. doi: 10.1016/j.brainresbull.2003.12.003.
Complexins (CPLXs) are small isomeric proteins that bind to the soluble NSF-attachment protein receptor (SNARE) complex and modulate neurotransmitter release. Two isoforms of CPLX exist in the brain, CPLXI and CPLXII. These are differentially distributed in the cortex and cerebellum, with CPLXI found in axosomatic terminals and CPLXII in axodendritic terminals. Since in cortex and cerebellum axosomatic terminals are inhibitory and axodendritic terminals are excitatory, it has been assumed that CPLXI modulates inhibitory and CPLXII modulates excitatory transmitter release. Here we used in situ hybridisation to study the mRNA distribution of CPLXI and CPLXII in mouse brain. We show that while CPLXs are expressed in distinct cell populations, they do not segregate with either particular neurotransmitters, or different classes of transmitter action. For example, while CPLXII is the dominant isoform in the output (glutamatergic excitatory) neurons of the cortex, it is also the dominant isoform in medium spiny (GABAergic inhibitory) neurons of the striatum. We suggest that the functional role of CPLXs depends not only on the identity of the neurotransmitter, but also upon the circuitry connecting the neurons in which they are expressed. Thus, the predominant expression of CPLXII in neurons of the basal ganglia and cortex suggests a role in cognition, emotional behaviour and control of voluntary movement, while the pattern of CPLXI expression suggests a primary role in motor learning programs and sensory processing.
复合体蛋白(CPLXs)是一类小分子异构体蛋白,它们与可溶性NSF附着蛋白受体(SNARE)复合体结合并调节神经递质释放。大脑中存在两种CPLX异构体,即CPLXI和CPLXII。它们在皮质和小脑中的分布不同,CPLXI存在于轴体终末,CPLXII存在于轴树突终末。由于在皮质和小脑中轴体终末是抑制性的,轴树突终末是兴奋性的,因此人们认为CPLXI调节抑制性神经递质释放,而CPLXII调节兴奋性神经递质释放。在这里,我们使用原位杂交技术研究CPLXI和CPLXII在小鼠脑中的mRNA分布。我们发现,虽然CPLXs在不同的细胞群体中表达,但它们并不与特定的神经递质或不同类型的递质作用相关联。例如,虽然CPLXII是皮质输出(谷氨酸能兴奋性)神经元中的主要异构体,但它也是纹状体中等棘状(γ-氨基丁酸能抑制性)神经元中的主要异构体。我们认为,CPLXs的功能作用不仅取决于神经递质的特性,还取决于表达它们的神经元之间的连接回路。因此,CPLXII在基底神经节和皮质神经元中的主要表达表明其在认知、情绪行为和自主运动控制中发挥作用,而CPLXI的表达模式表明其在运动学习程序和感觉处理中起主要作用。