Feldman D E, Knudsen E I
Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305, USA.
J Neurosci. 1998 Apr 15;18(8):3073-87. doi: 10.1523/JNEUROSCI.18-08-03073.1998.
Neural tuning for interaural time difference (ITD) in the optic tectum of the owl is calibrated by experience-dependent plasticity occurring in the external nucleus of the inferior colliculus (ICX). When juvenile owls are subjected to a sustained lateral displacement of the visual field by wearing prismatic spectacles, the ITD tuning of ICX neurons becomes systematically altered; ICX neurons acquire novel auditory responses, termed "learned responses," to ITD values outside their normal, pre-existing tuning range. In this study, we compared the glutamatergic pharmacology of learned responses with that of normal responses expressed by the same ICX neurons. Measurements were made in the ICX using iontophoretic application of glutamate receptor antagonists. We found that in early stages of ITD tuning adjustment, soon after learned responses had been induced by experience-dependent processes, the NMDA receptor antagonist D, L-2-amino-5-phosphonopentanoic acid (AP-5) preferentially blocked the expression of learned responses of many ICX neurons compared with that of normal responses of the same neurons. In contrast, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked learned and normal responses equally. After long periods of prism experience, preferential blockade of learned responses by AP-5 was no longer observed. These results indicate that NMDA receptors play a preferential role in the expression of learned responses soon after these responses have been induced by experience-dependent processes, whereas later in development or with additional prism experience (we cannot distinguish which), the differential NMDA receptor-mediated component of these responses disappears. This pharmacological progression resembles the changes that occur during maturation of glutamatergic synaptic currents during early development.
猫头鹰视顶盖中用于双耳时间差（ITD）的神经调谐是通过下丘外侧核（ICX）中依赖经验的可塑性来校准的。当幼年猫头鹰佩戴棱镜眼镜使视野持续发生侧向位移时，ICX神经元的ITD调谐会系统性地改变；ICX神经元会对超出其正常、先前存在的调谐范围的ITD值获得新的听觉反应，即“习得反应”。在本研究中，我们比较了习得反应与同一ICX神经元所表达的正常反应的谷氨酸能药理学特性。使用谷氨酸受体拮抗剂的离子电泳应用在ICX中进行测量。我们发现，在ITD调谐调整的早期阶段，即在依赖经验的过程诱导出习得反应后不久，与同一神经元的正常反应相比，NMDA受体拮抗剂D，L - 2 - 氨基 - 5 - 膦酰基戊酸（AP - 5）优先阻断了许多ICX神经元习得反应的表达。相比之下，非NMDA受体拮抗剂6 - 氰基 - 7 - 硝基喹喔啉 - 2,3 - 二酮（CNQX）对习得反应和正常反应的阻断作用相同。经过长时间的棱镜体验后，则不再观察到AP - 5对习得反应的优先阻断作用。这些结果表明，NMDA受体在依赖经验的过程诱导出习得反应后不久，在习得反应的表达中起优先作用，而在发育后期或有更多棱镜体验时（我们无法区分是哪种情况），这些反应中由NMDA受体介导的差异成分消失了。这种药理学进展类似于早期发育过程中谷氨酸能突触电流成熟期间发生的变化。
