RELATIONSHIP OF CANNABINOID CB1 RECEPTOR AND CHOLECYSTOKININ IMMUNOREACTIVITY IN MONKEY DORSOLATERAL PREFRONTAL CORTEX
RELATIONSHIP OF CANNABINOID CB1 RECEPTOR AND CHOLECYSTOKININ IMMUNOREACTIVITY IN MONKEY DORSOLATERAL PREFRONTAL CORTEX
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DOI：
10.1016/j.neuroscience.2010.06.011
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发表时间：
2010-09-15
期刊：
影响因子：
3.3
通讯作者：
Lewis, D. A.
中科院分区：
文献类型：
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作者：
Eggan, S. M.;Melchitzky, D. S.;Lewis, D. A.
接触大麻会损害依赖于背外侧前额叶皮层（DLPFC）回路的认知功能，并增加患精神分裂症的风险。大麻的作用是通过脑大麻素1受体（CB 1 R）介导的，在啮齿动物中，CB 1 R主要定位于含有胆囊收缩素（CCK）的皮质GABA篮神经元的轴突末端。CB 1 R-免疫反应（IR）轴突的层状分布在啮齿动物和猴子的新皮质之间的差异已被报道，这表明含有CB 1 R的细胞类型和CB 1 R-IR轴突终末的突触靶点可能在不同物种之间存在差异;然而，在灵长类动物DLPFC中，CB 1 R与含有CCK的中间神经元的关系以及CB 1 R和CCK轴突终末的突触后靶点均未被研究。因此，我们比较了分布模式的CB 1 R和CCK-IR结构，确定的比例CB 1 R和CCK神经元的双标记，并确定突触类型和突触后靶点的CB 1 R和CCK-IR轴突终末在猕猴DLPFC。通过光学显微镜，CB 1 R-和CCK-IR轴突表现出类似的层状分布，其最大密度在第4层。双标记荧光实验表明，91%的CB 1 R-IR神经元呈CCK免疫阳性，而只有51%的CCK-IR神经元呈CB 1 R免疫阳性。电镜下，CB 1 R-IR轴突终末形成的突触均为对称性突触，而CCK-1 R轴突终末形成的突触既有对称性突触（88%），也有不对称性突触（12%）。形成对称突触的CB 1 R和CCK-1 R轴突终末的主要突触后靶点是树突轴（81-88%），其余靶点是细胞体或树突棘。因此，尽管在层状分布的物种差异，CB 1 Rs主要定位于CCK篮神经元轴突在啮齿动物新皮层和猴DLPFC。这些轴突瞄准锥体神经元的体周区域，为与大麻使用和精神分裂症相关的DLPFC功能受损提供了潜在的解剖学基底。由Elsevier Ltd代表IBRO出版。
Exposure to cannabis impairs cognitive functions reliant on the circuitry of the dorsolateral prefrontal cortex (DLPFC) and increases the risk of schizophrenia. The actions of cannabis are mediated via the brain cannabinoid 1 receptor (CB1R), which in rodents is heavily localized to the axon terminals of cortical GABA basket neurons that contain cholecystokinin (CCK). Differences in the laminar distribution of CB1R-immunoreactive (IR) axons have been reported between rodent and monkey neocortex, suggesting that the cell type(s) containing CB1Rs, and the synaptic targets of CB1R-IR axon terminals, may differ across species; however, neither the relationship of CB1Rs to CCK-containing interneurons, nor the postsynaptic targets of CB1R and CCK axon terminals, have been examined in primate DLPFC. Consequently, we compared the distribution patterns of CB1R- and CCK-IR structures, determined the proportions of CB1R and CCK neurons that were dual-labeled, and identified the synaptic types and postsynaptic targets of CB1R- and CCK-IR axon terminals in macaque monkey DLPFC. By light microscopy, CB1R- and CCK-IR axons exhibited a similar laminar distribution, with their greatest densities in layer 4. Dual-label fluorescence experiments demonstrated that 91% of CB1R-IR neurons were immunopositive for CCK, whereas only 51% of CCK-IR neurons were immunopositive for CB1R. By electron microscopy, all synapses formed by CB1R-IR axon terminals were symmetric, whereas CCK-IR axon terminals formed both symmetric (88%) and asymmetric (12%) synapses. The primary postsynaptic target of both CB1R- and CCK-IR axon terminals forming symmetric synapses was dendritic shafts (81-88%), with the remainder targeting cell bodies or dendritic spines. Thus, despite species differences in laminar distribution, CB1Rs are principally localized to CCK basket neuron axons in both rodent neocortex and monkey DLPFC. These axons target the perisomatic region of pyramidal neurons, providing a potential anatomical substrate for the impaired function of the DLPFC associated with cannabis use and schizophrenia. Published by Elsevier Ltd on behalf of IBRO.