Region-Specific Disruption of Adenylate Cyclase Type 1 Gene Differentially Affects Somatosensorimotor Behaviors in Mice(1,2,3).
Region-Specific Disruption of Adenylate Cyclase Type 1 Gene Differentially Affects Somatosensorimotor Behaviors in Mice(1,2,3).
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DOI：
10.1523/eneuro.0007-14.2014
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发表时间：
2014-11
期刊：
影响因子：
3.4
通讯作者：
Erzurumlu RS
中科院分区：
文献类型：
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作者：
Arakawa H;Akkentli F;Erzurumlu RS
神经元特异性钙刺激的腺苷环化酶1(AC1)对于完善大脑的地形图是重要的。AC1在躯体感觉通路的所有水平上都有表达，全局或区域特异性基因缺失会导致不同的模式表型。区域特异性腺酰环化酶1(AC1)功能的丧失对小鼠的构图和感觉运动行为都有不同的影响。AC1在躯体感觉通路的所有水平上都有表达，并在地形图的精细化和图案化中起着重要作用。皮层特异性AC1功能丧失(CxAC1KO小鼠)不会影响桶图案和与刺激胡须相对应的特定桶的激活，也不会损害感觉运动行为。虽然全局性(AC1KO)和丘脑特异性(ThAC1KO)AC1功能丧失导致桶状图案的缺失，但选择性胡须刺激激活了局部对齐的皮质基因座。尽管胡须桶皮质有功能性的地形图，但感觉运动和社会行为受到损害，这表明在新皮质中地形图的图案化是重要的。腺苷环化酶I型(AC1)主要在大脑中表达，而且含量丰富。细胞内钙/钙调素的增加以一种活性依赖的方式调节AC1。在刺激下，AC1产生cAMP，它参与神经回路的构型和精炼。在小鼠中，编码AC1的Adcy1基因的自发突变或定向缺失会导致神经元模式形成缺陷。在初级躯体感觉(SI)皮层的神经模块中，代表口鼻上胡须的地形分布的桶未能形成。皮层或丘脑特异的Adcy1缺失导致不同的皮质模式表型，丘脑特异的干扰表型更为严重。尽管在“无桶”/Adcy1基因缺失的小鼠中没有桶，但丘脑皮质终末的密度和胡须刺激后皮质区的激活大致是地形图。大脑皮层体感躯体地图的图案化在多大程度上对感觉运动行为起作用？在这项研究中，我们在一系列感觉运动和社会行为测试中测试了AC1功能整体、皮质或丘脑丧失的小鼠，并将它们与剪掉所有胡须的小鼠进行了比较。与AC1功能的任何区域性或全局性破坏将导致相似的行为表型的直觉预期相反，我们发现这些菌株之间的损害程度存在显著差异。
The neuron-specific calcium-stimulated adenylate cyclase 1 (AC1) is important for refinement of topographic maps in the brain. AC1 is expressed at all levels of the somatosensory pathway and global or region-specific gene deletions lead to differential pattern phenotypes. Region-specific adenylyl cyclase 1 (AC1) loss of function differentially affects both patterning and sensorimotor behaviors in mice. AC1 is expressed at all levels of the somatosensory pathway and plays a major role in refinement and patterning of topographic sensory maps. Cortex-specific AC1 loss of function (CxAC1KO mice) does not affect barrel patterning and activation of specific barrels corresponding to stimulated whiskers and does not impair sensorimotor behaviors. While global (AC1KO) and thalamus-specific (ThAC1KO) AC1 loss of function leads to absence of barrel patterns, selective whisker stimulation activates topographically aligned cortical loci. Despite functional topography of the whisker-barrel cortex, sensorimotor and social behaviors are impaired, indicating the importance of patterning of topographical sensory maps in the neocortex. Adenylate cyclase type I (AC1) is primarily, and, abundantly, expressed in the brain. Intracellular calcium/calmodulin increases regulate AC1 in an activity-dependent manner. Upon stimulation, AC1 produces cAMP and it is involved in the patterning and the refinement of neural circuits. In mice, spontaneous mutations or targeted deletion of the Adcy1 gene, which encodes AC1, resulted in neuronal pattern formation defects. Neural modules in the primary somatosensory (SI) cortex, the barrels, which represent the topographic distribution of the whiskers on the snout, failed to form. Cortex- or thalamus-specific Adcy1 deletions led to different cortical pattern phenotypes, with thalamus-specific disruption phenotype being more severe. Despite the absence of barrels in the “barrelless”/Adcy1 null mice, thalamocortical terminal bouton density and activation of cortical zones following whisker stimulation were roughly topographic. To what extent does patterning of the cortical somatosensory body map play a role in sensorimotor behaviors? In this study, we tested mice with global, cortical, or thalamic loss of AC1 function in a battery of sensorimotor and social behavior tests and compared them to mice with all of the whiskers clipped. Contrary to intuitive expectations that any region-specific or global disruption of the AC1 function would lead to similar behavioral phenotypes, we found significant differences in the degree of impairment between these strains.