Brimblecombe Katherine R, Cragg Stephanie J
Department of Physiology, Anatomy and Genetics and.
Department of Physiology, Anatomy and Genetics and Oxford Parkinson's Disease Centre, University of Oxford, OX1 3PT, United Kingdom
J Neurosci. 2015 Jun 17;35(24):9017-23. doi: 10.1523/JNEUROSCI.0870-15.2015.
The mammalian striatum has a topographical organization of input-output connectivity, but a complex internal, nonlaminar neuronal architecture comprising projection neurons of two types interspersed among multiple interneuron types and potential local neuromodulators. From this cellular melange arises a biochemical compartmentalization of areas termed striosomes and extrastriosomal matrix. The functions of these compartments are poorly understood but might confer distinct features to striatal signal processing and be discretely governed. Dopamine transmission occurs throughout striosomes and matrix, and is reported to be modulated by the striosomally enriched neuromodulator substance P. However, reported effects are conflicting, ranging from facilitation to inhibition. We addressed whether dopamine transmission is modulated differently in striosome-matrix compartments by substance P.We paired detection of evoked dopamine release at carbon-fiber microelectrodes in mouse striatal slices with subsequent identification of the location of recording sites with respect to μ-opioid receptor-rich striosomes. Substance P had bidirectional effects on dopamine release that varied between recording sites and were prevented by inhibition of neurokinin-1 receptors. The direction of modulation was determined by location within the striosomal-matrix axis: dopamine release was boosted in striosome centers, diminished in striosomal-matrix border regions, and unaffected in the matrix. In turn, this different weighting of dopamine transmission by substance P modified the apparent center-surround contrast of striosomal dopamine signals. These data reveal that dopamine transmission can be differentially modulated within the striosomal-matrix axis, and furthermore, indicate a functionally distinct zone at the striosome-matrix interface, which may have key impacts on striatal integration.
哺乳动物的纹状体具有输入-输出连接的拓扑组织，但内部神经元结构复杂，无分层，由两种类型的投射神经元散布在多种中间神经元类型和潜在的局部神经调质之间组成。从这种细胞混合物中，出现了称为纹状体小体和纹状体基质的区域的生化分隔。这些分隔的功能尚不清楚，但可能赋予纹状体信号处理不同的特征并受到离散控制。多巴胺传递发生在整个纹状体小体和基质中，据报道受纹状体中富集的神经调质P物质的调节。然而，报道的效应相互矛盾，从促进到抑制不等。我们研究了P物质是否在纹状体小体-基质分隔中对多巴胺传递进行不同的调节。我们将小鼠纹状体切片中碳纤维微电极诱发的多巴胺释放检测与随后确定记录位点相对于富含μ-阿片受体的纹状体小体的位置配对。P物质对多巴胺释放有双向作用，在记录位点之间有所不同，并可通过抑制神经激肽-1受体来阻止。调节方向由纹状体小体-基质轴内的位置决定：多巴胺释放在纹状体小体中心增强，在纹状体小体-基质边界区域减弱，在基质中不受影响。反过来，P物质对多巴胺传递的这种不同权重改变了纹状体小体多巴胺信号明显的中心-周边对比度。这些数据表明，多巴胺传递可以在纹状体小体-基质轴内受到不同的调节，此外，还表明在纹状体小体-基质界面存在一个功能上不同的区域，这可能对纹状体整合产生关键影响。
