[通过条件转基因方法改变神经网络:我们理解基底神经节系统神经精神疾病的关键]。

S N Schiffmann
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引用次数: 0

摘要

纹状体是基底神经节系统的第一个中继,在运动功能和动机过程中起关键作用。背侧纹状体是运动控制和运动学习的中心,而腹侧纹状体或伏隔核对动机、奖励系统和药物强化至关重要。该系统在帕金森病和亨廷顿病等运动障碍以及包括药物成瘾在内的精神障碍中功能失调。纹状体由基底神经节回路中两条不同通路起源处的两群神经元和不同群的中间神经元组成。纹状体和纹状体神经元这两种输出神经元的特征在于它们的投射位点以及它们在多巴胺受体和神经肽中的差异表达。它们在运动控制和动机过程中的作用以及在系统病理中的神经适应机制中的作用仍然未知。为了确定这些特定的功能,我们通过有条件的转基因方法开发了新的动物模型,这些模型带有分子或细胞“损伤”,以针对特定的神经元群体。通过这种方法,我们证明了纹状体神经元群在运动控制和药物成瘾过程中的抑制作用,发现了纹状体神经元选择性表达的新基因,这些基因可能成为未来治疗的靶点,并确定了这群神经元紊乱在注意缺陷多动障碍(ADHD)中的潜在作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Changes in neural networks by conditional transgenic approach: a key to our comprehension of neuro-psychiatric disorders in the basal ganglia system].

The striatum, the first relay of the basal ganglia system, is critically involved in motor functions and motivational processes. The dorsal striatum is central to the motor control and motor learning and the ventral striatum or nucleus accumbens is essential for motivation, the reward system and reinforcement by drugs. This system is dysfunctional in movement disorders such as Parkinson's disease and Huntington's disease and in psychiatric disorders including drug addiction. The striatum consists of two populations of neurons projecting at the origin of two distinct paths in the circuit of basal ganglia, and of different populations of interneurons. These two populations of efferent neurons, striatopallidal and striatonigral neurons, are characterized by their projection sites and their differential expression in dopamine receptors and neuropeptides. Their roles in motor control and motivational processes and in the mechanisms of neuroadaptation in the system's pathologies remain mostly unknown. To identify these specific functions, we have developed new animal models wearing molecular or cell "lesions" by a conditional transgenic approach to target a specific population of neurons. By this approach, we demonstrated the inhibitory role of the population of striatopallidal neurons in the motor control and in the process of drug addiction, identified new genes selectively expressed by striatopallidal neurons that could be the target for future therapies and identified the potential role of this population of neurons disturbances in attention-deficit hyperactivity disorder (ADHD).

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