Barrel map development relies on protein kinase a regulatory subunit IIβ-mediated cAMP signaling
Barrel map development relies on protein kinase a regulatory subunit IIβ-mediated cAMP signaling
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DOI：
10.1523/jneurosci.3745-05.2006
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发表时间：
2006-04-19
影响因子：
5.3
通讯作者：
Crair, MC
中科院分区：
文献类型：
--
作者：
Inan, M;Lu, HC;Crair, MC
介导大脑回路活动依赖性发育的细胞和分子机制仍然不完全清楚。在这里，我们研究cAMP依赖性蛋白激酶[蛋白激酶A（PKA）]信号在皮质发育和可塑性的作用，专注于其在丘脑皮质突触和桶地图发展的作用。我们提供了直接的证据，PKA活性介导桶地图的形成，使用敲除小鼠，缺乏II型β调节亚基PKA（PKARII β）。我们发现，PKARII β介导的PKA功能是必要的适当的树突状细胞和组织的皮质第四层神经元成桶，但不为发展和可塑性的丘脑皮质传入集群成桶模式。我们将PKARII β功能定位于桶状皮质的突触后过程，并表明突触后PKA靶点（而非突触前PKA靶点）在pkar 2b敲除（PKARII β（-/-））小鼠中具有降低的磷酸化。我们还表明，TC突触的长时程增强以及这些突触处AMPA受体功能的相关发育增加（通常以桶形式发生）在PKARII β（-/-）小鼠中不存在。总之，这些实验支持桶地图开发的活性依赖性模型，其中基于突触形成的Hebbian机制的丘脑皮质突触的选择性添加和消除由依赖于PKARII β功能的cAMP/PKA依赖性途径介导。
The cellular and molecular mechanisms mediating the activity-dependent development of brain circuitry are still incompletely understood. Here, we examine the role of cAMP-dependent protein kinase [ protein kinase A (PKA)] signaling in cortical development and plasticity, focusing on its role in thalamocortical synapse and barrel map development. We provide direct evidence that PKA activity mediates barrel map formation using knock-out mice that lack typeII beta regulatory subunits of PKA (PKARII beta). We show that PKARII beta mediated PKA function is required for proper dendritogenesis and the organization of cortical layer IV neurons into barrels, but not for the development and plasticity of thalamocortical afferent clustering into a barrel pattern. We localize PKARII beta function to postsynaptic processes in barrel cortex and show that postsynaptic PKA targets, but not presynaptic PKA targets, have decreased phosphorylation in pkar2b knock-out (PKARII beta(-/-)) mice. We also show that long-term potentiation at TC synapses and the associated developmental increase in AMPA receptor function at these synapses, which normally occurs as barrels form, is absent in PKARII beta(-/-) mice. Together, these experiments support an activity-dependent model for barrel map development in which the selective addition and elimination of thalamocortical synapses based on Hebbian mechanisms for synapse formation is mediated by a cAMP/PKA-dependent pathway that relies on PKARII beta function.