Cui Changhai, Booker T K, Allen Roberta S, Grady Sharon R, Whiteaker Paul, Marks Michael J, Salminen Outi, Tritto Theresa, Butt Christopher M, Allen W R, Stitzel Jerry A, McIntosh J Michael, Boulter Jim, Collins Allan C, Heinemann Stephen F
Salk Institute for Biological Studies, La Jolla, California 92037-1099, USA.
J Neurosci. 2003 Dec 3;23(35):11045-53. doi: 10.1523/JNEUROSCI.23-35-11045.2003.
Nigrostriatal dopaminergic neurons express many nicotinic acetylcholine receptor (nAChR) subunits capable of forming multiple nAChR subtypes. These subtypes are expressed differentially along the neuron and presumably mediate diverse responses. beta3 subunit mRNA has restricted expression but is abundant in the substantia nigra and ventral tegmental areas. To investigate the potential role(s) of nicotinic receptors containing the beta3 subunit in dopaminergic tracts, we generated mice with a null mutation in the beta3 gene. We were thereby able to identify a population of beta3-dependent alpha-conotoxin MII-binding nAChRs that modulate striatal dopamine release. Changes were also observed in locomotor activity and prepulse inhibition of acoustic startle, behaviors that are controlled, in part, by nigrostriatal and mesolimbic dopaminergic activity, respectively, suggesting that beta3-containing nAChRs modulate these behaviors.
黑质纹状体多巴胺能神经元表达许多能够形成多种烟碱型乙酰胆碱受体（nAChR）亚型的烟碱型乙酰胆碱受体亚基。这些亚型沿神经元呈差异性表达，推测介导多种反应。β3亚基mRNA表达受限，但在黑质和腹侧被盖区含量丰富。为了研究含β3亚基的烟碱型受体在多巴胺能神经通路中的潜在作用，我们培育出β3基因发生无效突变的小鼠。借此，我们能够鉴定出一群依赖β3的α-芋螺毒素MII结合型nAChR，它们可调节纹状体多巴胺释放。在运动活性和听觉惊吓的前脉冲抑制方面也观察到了变化，这两种行为分别部分受黑质纹状体和中脑边缘多巴胺能活性控制。这表明含β3的nAChR可调节这些行为。
