Thalamic adenylyl cyclase 1 is required for barrel formation in the somatosensory cortex.
Thalamic adenylyl cyclase 1 is required for barrel formation in the somatosensory cortex.
复制标题
丘脑腺苷酸环化酶1是体感皮质中桶形形成所必需的。
DOI：
10.1016/j.neuroscience.2015.01.043
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发表时间：
2015-04-02
期刊：
影响因子：
3.3
通讯作者：
Iwasato T
中科院分区：
文献类型：
--
作者：
Suzuki A;Lee LJ;Hayashi Y;Muglia L;Itohara S;Erzurumlu RS;Iwasato T
环AMP信号传导对于神经元回路的活性依赖性细化是至关重要的。腺苷酸环化酶1（AC 1），主要的钙/钙调素刺激的腺苷酸环化酶在大脑中的全球中断，损害的胡须相关的离散神经模块（桶）在小鼠皮层第4层的形成。由于AC 1在丘脑和新皮质中表达，因此出现了突触前或突触后（或两者）AC 1在桶形成中发挥作用的问题。以前，我们产生了皮质特异性AC 1敲除（Cx-AC 1 KO）小鼠，并发现这些动物发展组织学正常桶，这表明丘脑AC 1在桶形成中可能发挥更突出的作用。为了确定这一点，我们产生了三种新的小鼠品系：其中一种是AC 1在近一半的丘脑腹侧基底核细胞中被破坏，除了皮质兴奋性神经元（Cx/pTh-AC 1 KO小鼠），另一种是AC 1在丘脑中被破坏，但不在皮层或脑干躯体感觉系统（Th-AC 1 KO小鼠）。Cx/pTh-AC 1 KO小鼠在桶形成方面表现出严重缺陷。Th-AC 1 KO小鼠在桶图案中显示出甚至更严重的破坏。在这两条线，单丘脑皮质（TC）轴突标记显示了更大的横向范围的TC轴突在第4层相比，控制。在第三行中，所有钙刺激的腺苷酸环化酶（AC 1和AC 8）在皮层兴奋性神经元中被删除。这些老鼠有正常的桶。总之，这些结果表明，丘脑AC 1在小鼠TC电路的模式化和细化中起着重要作用。
Cyclic AMP signaling is critical for activity-dependent refinement of neuronal circuits. Global disruption of adenylyl cyclase 1 (AC1), the major calcium/calmodulin-stimulated adenylyl cyclase in the brain, impairs formation of whisker-related discrete neural modules (the barrels) in cortical layer 4 in mice. Since AC1 is expressed both in the thalamus and the neocortex, the question of whether pre-or postsynaptic (or both) AC1 plays a role in barrel formation has emerged. Previously, we generated cortex-specific AC1 knockout (Cx-AC1KO) mice and found that these animals develop histologically normal barrels, suggesting a potentially more prominent role for thalamic AC1 in barrel formation. To determine this, we generated three new lines of mice: one in which AC1 is disrupted in nearly half of the thalamic ventrobasal nucleus cells in addition to the cortical excitatory neurons (Cx/pTh-AC1KO mouse), and another in which AC1 is disrupted in the thalamus but not in the cortex or brainstem nuclei of the somatosensory system (Th-AC1KO mouse). Cx/pTh-AC1KO mice show severe deficits in barrel formation. Th-AC1KO mice show even more severe disruption in barrel patterning. In these two lines, single thalamocortical (TC) axon labeling revealed a larger lateral extent of TC axons in layer 4 compared to controls. In the third line, all calcium-stimulated adenylyl cyclases (both AC1 and AC8) are deleted in cortical excitatory neurons. These mice have normal barrels. Taken together, these results indicate that thalamic AC1 plays a major role in patterning and refinement of the mouse TC circuitry.
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