Cre recombinase mediated deletion of BDNF in dopamine neurons

我们建立了一种小鼠模型，其中多巴胺神经元缺乏合成BDNF(BDNF基因敲除小鼠)的能力，通过在BDNFloxP转基因小鼠中表达Cre重组酶来表达Cre重组酶。这个小鼠模型提供了一个工具来确定专门在DA神经元中合成的BDNF是如何对多巴胺能系统的形成和功能做出贡献的。脑源性神经营养因子在中脑DA神经元中高表达，作为一种分泌型分子，可作为旁分泌因子作用于DA神经元，也可通过顺行转运作用于周围神经元和靶区。我们打算利用BDNF基因敲除的小鼠模型来确定去掉DA神经元中的BDNF如何影响发育过程中和成年动物中脑多巴胺能神经传递的状态。此外，由于BDNF在DA神经元中的表达已经被证明塑造了在学习和奖赏过程中观察到的神经可塑性，我们打算确定在DA神经元中缺乏BDNF可能如何影响与奖赏系统相关的行为输出，并确定BDNF表达可能直接影响DA神经元固有的哪些细胞机制和通路。

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.