Cre recombinase mediated deletion of BDNF in dopamine neurons

我们已经开发了一种小鼠模型，其中多巴胺神经元缺乏合成BDNF的能力（BDNF敲除小鼠），通过表达Cre重组酶通过多巴胺转运蛋白基因座在BDNF loxP转基因小鼠。 这种小鼠模型提供了一种工具，以确定如何BDNF合成专门在DA神经元有助于多巴胺能系统的形成和功能。BDNF在中脑DA能神经元中高度表达，作为一种分泌分子，它可以作用于DA能神经元，作为旁分泌因子，或通过顺行运输对周围神经元和靶区域产生影响。 我们打算利用BDNF基因敲除小鼠模型，以确定如何在DA神经元的BDNF消融影响中脑多巴胺能神经传递的状态在发展过程中，并在成年动物。 此外，在DA神经元中的BDNF的表达已被证明塑造在学习和奖励过程中观察到的神经可塑性，我们打算定义如何缺乏BDNF专门在DA神经元可能会影响行为输出相关的奖励系统，并定义什么样的细胞机制和DA神经元固有的途径可能会直接受到BDNF表达的影响。

We have developed a mouse model in which dopamine neurons lack the ability to synthesize BDNF (BDNF knockout mice), by expressing Cre recombinase through the dopamine transporter locus in a BDNF loxP transgenic mouse. This mouse model provides a tool to determine how BDNF synthesized exclusively in DA neurons contributes to the shaping and function of the dopaminergic system. BDNF is highly expressed in midbrain DA neurons, and as a secreted molecule it could act on DA neurons, as a paracrine factor, or have an effect on surrounding neurons and in target areas by anterograde transport. We intend to utilize the BDNF knockout mouse model to determine how the ablation of BDNF in DA neurons affects the state of midbrain dopaminergic neurotransmission during development and in adult animals. In addition, as expression of BDNF in DA neurons has been shown to shape the neuro-plasticity observed during learning and reward, we intend to define how the lack of BDNF exclusively in DA neurons may affect behavioral outputs related to the reward system, and to define what cellular mechanisms and pathways intrinsic to DA neurons may be directly affected by BDNF expression.