Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA.
J Neurosci. 2011 Nov 2;31(44):15727-31. doi: 10.1523/JNEUROSCI.3875-11.2011.
Fast-spiking interneurons (FSIs) can exert powerful control over striatal output, and deficits in this cell population have been observed in human patients with Tourette syndrome and rodent models of dystonia. However, a direct experimental test of striatal FSI involvement in motor control has never been performed. We applied a novel pharmacological approach to examine the behavioral consequences of selective FSI suppression in mouse striatum. IEM-1460, an inhibitor of GluA2-lacking AMPARs, selectively blocked synaptic excitation of FSIs but not striatal projection neurons. Infusion of IEM-1460 into the sensorimotor striatum reduced the firing rate of FSIs but not other cell populations, and elicited robust dystonia-like impairments. These results provide direct evidence that hypofunction of striatal FSIs can produce movement abnormalities, and suggest that they may represent a novel therapeutic target for the treatment of hyperkinetic movement disorders.
快速棘突神经元（FSIs）可以对纹状体的输出施加强大的控制，并且在人类抽动秽语综合征患者和运动障碍的啮齿动物模型中已经观察到这种细胞群体的缺陷。然而，对纹状体 FSI 参与运动控制的直接实验测试从未进行过。我们应用了一种新的药理学方法来研究选择性抑制 FSIs 在小鼠纹状体中的行为后果。IEM-1460 是一种缺乏 GluA2 的 AMPAR 抑制剂，选择性地阻断了 FSIs 的突触兴奋，但不阻断纹状体投射神经元的兴奋。将 IEM-1460 注入感觉运动纹状体减少了 FSIs 的放电率，但不影响其他细胞群体，并引起了强烈的类似肌张力障碍的损伤。这些结果提供了直接的证据，表明纹状体 FSIs 的功能低下会导致运动异常，并表明它们可能成为治疗运动过度障碍的新的治疗靶点。
