The functional analysis of interneurons in central nervus system.

1. 利用免疫毒素介导的细胞靶向技术（IMCT），通过选择性消除视网膜胆碱能中间神经元即星爆细胞，研究了定向选择性的细胞来源和机制。视网膜星爆细胞消融不仅破坏了神经节细胞反应的定向选择性，而且破坏了刺激运动引起的眼动反射。因此，星爆细胞是通过综合突触传递辨别刺激运动方向的关键因素，并在稳定图像运动的信息处理中发挥关键作用。用IMCT研究纹状体胆碱能中间神经元的生理作用。单侧胆碱能细胞消融引起急性异常转向行为。这些小鼠表现出逐渐恢复，但由于过度刺激和抑制多巴胺的作用而表现出异常的转向。急性期，分别通过刺激纹状体神经元和抑制纹状体顶神经元，基底神经节功能转变为多活动状态。D1和D2多巴胺受体下调，减轻了多巴胺主导的突触扰动，但在控制多巴胺反应方面留下了缺陷。长期接触可卡因会导致与可卡因强化和成瘾相关的长期行为改变。可卡因成瘾的重要神经基质是伏隔核（Nac）。尽管Nac的神经回路受其他几种神经递质控制，但它们与可卡因成瘾的关系仍然难以捉摸。我们用IMCT切除了成年Nac的胆碱能中间神经元，并研究了乙酰胆碱递质在与可卡因强化和成瘾相关的适应性行为改变中的作用。在双侧胆碱能细胞消除的小鼠中，慢性可卡因给药诱导了运动活动的显著和进行性增加。此外，与野生型的同伴相比，这些小鼠在较低剂量的可卡因下表现出强大的条件位置偏好。本研究表明，乙酰胆碱在Nac中起着关键作用。少

1. The cellular origin and mechanism of directional selectivity were investigated by selectively eliminating retinal cholinergic interneurons, namely starburst cells, using the immunotoxin-mediated cell targeting techniques (IMCT). Starburst cell ablation in the retina abolished not only directional selectivity of ganglion cell responses but also an optokinetic eye reflex derived by stimulus movement. Starburst cells therefore serve as the key element that discriminates the direction of stimulus movement through integrative synaptic transmission and play a pivotal role in information processing that stabilizes image motion.2. The physiological role of striatal cholinergic interneurons was investigated with IMCT. Unilateral cholinergic cell ablation caused an acute abnormal turning behavior. These mice showed gradual ecovery but displayed abnormal turning by both excess stimulation and inhibition of dopamine actions. In the acute phase, basal ganglia function was shifted to a hyperactiv … More e state by stimulation and suppression of striatonigral and striatopallidal neurons, respectively. D1 and D2 dopamine receptors were then down-regulated, relieving dopamine-predominant synaptic perturbation but leaving a defect in controlling dopamine responses.3. Chronic exposure to cocaine causes long-lasting behavioral changes associated with cocaine reinforcement and addiction. An important neural substrate for cocaine addiction is the nucleus accumbens (Nac). Although the neural circuit of the Nac is controlled by several other neurotransmitters, their involvement in cocaine addiction remains elusive. We ablated cholinergic interneurons from the adult Nac with IMCT and examined the role of acetylcholine transmitter in adaptive behavioral changes associated with cocaine reinforcement and addiction. In bilaterally cholinergic cell-eliminated mice, chronic cocaine administration induced a prominent and progressive increase in locomotor activity. Moreover, these mice showed robust conditioned place preference with a lower dose of cocaine, compared with wild-type littermates. This investigation demonstrates that acetylcholine in the Nac plays a key role in actions of cocaine. Less