Cre recombinase mediated deletion of BDNF in dopamine neurons

我们在BDNF loxP转基因小鼠中通过多巴胺转运位点表达Cre重组酶，建立了多巴胺神经元缺乏合成BDNF能力的小鼠模型（BDNF敲除小鼠）。该小鼠模型为确定仅在DA神经元中合成的BDNF如何参与多巴胺能系统的形成和功能提供了工具。BDNF在中脑DA神经元中高度表达，作为分泌分子可作用于DA神经元，作为旁分泌因子，或通过顺行转运作用于周围神经元和靶区。我们打算利用BDNF敲除小鼠模型来确定DA神经元中BDNF的消弭如何影响发育期间和成年动物中脑多巴胺能神经传递状态。此外，由于BDNF在DA神经元中的表达已被证明可以塑造学习和奖励过程中观察到的神经可塑性，我们打算确定DA神经元中缺乏BDNF如何影响与奖励系统相关的行为输出，并确定DA神经元固有的细胞机制和途径可能直接受到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.