Functional and structural specific roles of activity-driven BDNF within circuits formed by single spiny stellate neurons of the barrel cortex.
Functional and structural specific roles of activity-driven BDNF within circuits formed by single spiny stellate neurons of the barrel cortex.
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DOI：
10.3389/fncel.2014.00372
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发表时间：
2014
影响因子：
5.3
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Sun QQ;Zhang Z;Sun J;Nair AS;Petrus DP;Zhang C
脑源性神经营养因子（BDNF）在多种神经发育障碍和药物治疗中起关键作用。然而，目前还不清楚BDNF对不同电路组件的具体影响。目前的研究主要集中在BDNF在突触发育修饰中的作用。BDNF在体内完善功能回路中的确切作用尚不清楚。BDNF的Val 66 Met多态性可能与认知障碍的风险增加相关，并且至少部分地由BDNF的活动依赖性运输和/或分泌介导。使用缺乏活性驱动的BDNF表达的突变小鼠（bdnf-KIV），我们先前报道了皮质GABA能网络的经验调节是由活性驱动的BDNF表达介导的。在这里，我们证明了活动驱动的BDNF对第四层棘状星状细胞形成的电路的影响是高度特异性的。在结构上，突变体中的树突状而非轴突形态发生了改变。在生理上，GABA能突触而不是谷氨酸能突触受到严重影响。对GABA传递的影响通过突触前钙依赖性释放概率的改变而发生。这些结果表明，通过活动驱动的BDNF表达的神经元活动，可以选择性地调节在体内的IV层电路的特定功能。我们假设活性依赖性BDNF的作用是调节与增益控制相关的电路的计算能力（即，前馈抑制）;而与感觉通路相关的电路的基本布线被保留。皮层回路中的增益控制调制对认知加工和大脑状态转换具有广泛的影响。认知行为和模式是由大脑状态决定的，因此研究内源性BDNF对神经回路的改变，可以深入了解BDNF介导的疾病的细胞和分子机制。
Brain derived neurotrophic factor (BDNF) plays key roles in several neurodevelopmental disorders and actions of pharmacological treatments. However, it is unclear how specific BDNF’s effects are on different circuit components. Current studies have largely focused on the role of BDNF in modification of synaptic development. The precise roles of BDNF in the refinement of a functional circuit in vivo remain unclear. Val66Met polymorphism of BDNF may be associated with increased risk for cognitive impairments and is mediated at least in part by activity-dependent trafficking and/or secretion of BDNF. Using mutant mice that lacked activity-driven BDNF expression (bdnf-KIV), we previously reported that experience regulation of the cortical GABAergic network is mediated by activity-driven BDNF expression. Here, we demonstrate that activity-driven BDNF’s effects on circuits formed by the layer IV spiny stellate cells are highly specific. Structurally, dendritic but not axonal morphology was altered in the mutant. Physiologically, GABAergic but not glutamatergic synapses were severely affected. The effects on GABA transmission occurs via presynaptic alteration of calcium-dependent release probability. These results suggest that neuronal activity through activity-driven BDNF expression, can selectively regulate specific features of layer IV circuits in vivo. We postulate that the role of activity-dependent BDNF is to modulate the computational ability of circuits that relate to the gain control (i.e., feed-forward inhibition); whereas the basic wiring of circuits relevant to the sensory pathway is spared. Gain control modulation within cortical circuits has broad impact on cognitive processing and brain state-transitions. Cognitive behavior and mode is determined by brain states, thus the studying of circuit alteration by endogenous BDNF provides insights into the cellular and molecular mechanisms of diseases mediated by BDNF.
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影响因子：
64.8
作者：
COHENCORY, S;FRASER, SE
通讯作者：
FRASER, SE
DOI：
10.1073/pnas.1206492109
发表时间：
2012-11-20
影响因子：
11.1
作者：
English, Christopher N.;Vigers, Alison J.;Jones, Kevin R.
通讯作者：
Jones, Kevin R.
影响因子：
5.3
作者：
Genoud, C;Knott, GW;Welker, E
通讯作者：
Welker, E
影响因子：
16.2
作者：
Chang, QA;Khare, G;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
4.7
作者：
Deinhardt K;Chao MV
通讯作者：
Chao MV