Involvement of Protein Kinase A in Patterning of the Mouse Somatosensory Cortex
Involvement of Protein Kinase A in Patterning of the Mouse Somatosensory Cortex
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DOI：
10.1523/jneurosci.0750-06.2006
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发表时间：
2006-05
期刊：
影响因子：
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通讯作者：
Edinburgh Research Explorer;Ruth F. Watson;Raja' M. Abdel-Majid;M. Barnett;Brandon S. Willis;A. Katsnelson;T. Gillingwater;G. McKnight;P. Kind;P. Neumann
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文献类型：
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作者：
Edinburgh Research Explorer;Ruth F. Watson;Raja' M. Abdel-Majid;M. Barnett;Brandon S. Willis;A. Katsnelson;T. Gillingwater;G. McKnight;P. Kind;P. Neumann
由于“桶场”的存在，小鼠躯体感觉皮层的模式异常明显。突触前5-羟色胺和突触后谷氨酸受体调节桶的形成，但很少有人知道的细胞内信号通路，通过它们的行动。为了确定蛋白激酶A（PKA）是否在桶场的发展中发挥作用，我们研究了五个可行的PKA亚基特异性敲除（KO）小鼠品系的桶场异常。这些小鼠中存在桶，但与野生型动物相比，缺乏RIIβ亚基的小鼠显示桶中空和侧面细胞密度之间的对比度显著降低。后内侧桶分区的丘脑皮质传入分离似乎正常，表明RIIβ蛋白的突触后基因作用位点。免疫电镜证实RIIβ选择性地定位于树突和树突棘。缺乏RIIβ的小鼠显示谷氨酸受体A（GluRA）亚单位插入到出生后第7天体感皮层的突触后密度减少;然而，GluRA KO小鼠发育正常桶。我们的研究结果清楚地表明了突触后PKA信号通路在桶分化中的作用。他们还证明了一个明确的分离之间的调节GluRA贩运PKA和它的作用桶形成。最后，虽然不能排除PKA在cAMP下游的作用，但这些数据表明PKA可能不是主要的下游靶点，因为没有突变体显示类似于腺苷酸环化酶1型KO小鼠中观察到的无桶表型。这些结果提供了洞察活动依赖性机制，调节桶的形成。
Patterning of the mouse somatosensory cortex is unusually evident because of the presence of a “barrel field.” Presynaptic serotonin and postsynaptic glutamate receptors regulate barrel formation, but little is known of the intracellular signaling pathways through which they act. To determine whether protein kinase A (PKA) plays a role in the development of the barrel field, we examined five viable PKA subunit-specific knock-out (KO) mouse lines for barrel field abnormalities. Barrels are present in these mice, but those lacking the RIIβ subunit display significantly reduced contrast between the cell densities of barrel hollows and sides compared with wild-type animals. Thalamocortical afferent segregation in the posterior medial barrel subfield appeared normal, suggesting a postsynaptic site of gene action for the RIIβ protein. Immunoelectron microscopy confirmed that RIIβ was selectively localized to dendrites and dendritic spines. Mice lacking RIIβ show reduced glutamate receptor A (GluRA) subunit insertion into the postsynaptic density in postnatal day 7 somatosensory cortex; however, GluRA KO mice developed normal barrels. Our results clearly demonstrate a role for postsynaptic PKA signaling pathways in barrel differentiation. They also demonstrate a clear dissociation between the regulation of GluRA trafficking by PKA and its role in barrel formation. Finally, although a role for PKA downstream of cAMP cannot be ruled out, these data suggest that PKA may not be the principle downstream target because none of the mutants showed a barrelless phenotype similar to that observed in adenylate cyclase type 1 KO mice. These results give insight into activity-dependent mechanisms that regulate barrel formation.