Martin J H, Ghez C
Columbia University Center for Neurobiology and Behavior, and NYS Psychiatric Institute, New York, NY 10032-2695, USA.
J Neurosci Methods. 1999 Jan;86(2):145-59. doi: 10.1016/s0165-0270(98)00163-0.
In this review, we describe how pharmacological inactivation can be used to elucidate the central control of skilled limb movement. Local anesthetics and tetrodotoxin block neuronal cell bodies and passing fibers while gamma-aminobutyric acid (GABA) and muscimol only block cell bodies. Blockade induction time is short (several minutes) for all the agents. Blockade duration produced by local anesthetics and GABA is 15-60 min, while that of tetrodotoxin and muscimol is up to several days. We describe our drug injection system, with an integrated microelectrode and a viewing port for visually monitoring drug flow into the injection cannula. We used glucose metabolism to assess the extent of inactivation. Intracortical lidocaine or muscimol injection produces a central core of maximal hypometabolism (1 mm radius), which could be due to drug spread, surrounded by an extensive region (several millimeters) of reduced hypometabolism, possibly due to reduced synaptic activity of neurons receiving projections from the core region. Drug injection only depresses neuronal activity, which contrasts with cooling, where there can be neuronal hyperexcitability at the periphery of the inactivation site. Our experiments in behaving animals show how pharmacological inactivation is an effective analytical tool for dissecting the differential functional contributions of subcortical and cortical forelimb representations to limb movement control.
在本综述中，我们描述了如何利用药理学失活来阐明熟练肢体运动的中枢控制。局部麻醉药和河豚毒素可阻断神经元细胞体和传导纤维，而γ-氨基丁酸（GABA）和蝇蕈醇仅阻断细胞体。所有这些药物的阻断诱导时间都很短（几分钟）。局部麻醉药和GABA产生的阻断持续时间为15 - 60分钟，而河豚毒素和蝇蕈醇的阻断持续时间长达数天。我们描述了我们的药物注射系统，它集成了微电极和一个观察口，用于视觉监测药物流入注射套管的情况。我们利用葡萄糖代谢来评估失活的程度。皮层内注射利多卡因或蝇蕈醇会产生一个最大代谢减退的中心核心区域（半径1毫米），这可能是由于药物扩散所致，其周围是一个广泛的区域（几毫米），代谢减退程度较轻，这可能是由于接受来自核心区域投射的神经元的突触活动减少所致。药物注射只会抑制神经元活动，这与冷却形成对比，在冷却时失活部位的周边可能会出现神经元过度兴奋。我们在行为动物身上进行的实验表明，药理学失活是一种有效的分析工具，可用于剖析皮层下和皮层前肢表征对肢体运动控制的不同功能贡献。
