TRANSNEURONAL SIGNALS FOR AFFERENT REGULATION

传入活动已被证明可以调节许多性质， 突触后神经元 众所周知，传入输入调节神经元的活动， 突触后神经元的电活动， 神经传递素 然而，传入输入也调节代谢， 突触后神经元的活动，特别是在发育早期。 的 后一种形式的跨神经元调节的信号是未知的。 小鸡的脑干听觉系统已经被证明是一个有用的 用于研究细胞代谢跨神经元调节的系统。 耳蜗大细胞核（NM）内的二级听觉神经元 核）从同侧听觉接受唯一的兴奋性输入 神经。 消除一侧听神经的活动 大脑已经显示出改变NM神经元的许多特性。 为 例如，几天后，NM中的一部分神经元死亡， 其余的都缩小了。 听神经消失后早期 活动在年轻的小鸡，在NM神经元代谢的变化已经被 观察 例如，在1小时内， 通过脑同侧的NM神经元的蛋白质合成。 等 然而，未观察到NM神经元结构和功能的变化 在消除成年鸟类的听觉神经活动后。 拟议的实验调查参与调节的信号 的电活动和代谢活动。 这些实验将在幼鼠（1-2周龄）和 成年鸡（1岁） 电活动的调节是 首先通过分析不同组织的解剖分布来研究 兴奋性氨基酸受体的种类。 的生理效应 兴奋性氨基酸然后通过应用特定的 激动剂和拮抗剂，同时从NM神经元细胞内记录， 一种体外脑切片制备方法。 研究代谢调节 通过评估体外切片制备中蛋白质合成的变化， 经过各种治疗。 单侧刺激听神经 体外已经显示出在蛋白质合成中产生类似的变化， 在体内观察到的。 特异性激动剂和拮抗剂的应用 将评估不同类型的兴奋性氨基酸的相对作用 受体和第二信使系统在脑跨神经元调节中的作用 干听觉系统，2）负责信号的理解 该系统中神经元代谢的调节和3） 了解年龄相关的差异，这可能会导致年龄- 神经元对传入神经改变的敏感性依赖 活动

Afferent activity has been shown to regulate a number of properties of postsynaptic neurons. It is well known that afferent input regulates the electrical activity of postsynaptic neurons through the action of neurotransmitters. Afferent input, however, also regulates the metabolic activity of postsynaptic neurons, particularly early in development. The signals for this latter form of transneuronal regulation are not known. The brain stem auditory system of the chick has proven to be a useful system for investigation transneuronal regulation of cellular metabolism. Second-order auditory neurons in nucleus magnocellularis (NM, the cochlear nucleus) receive their sole excitatory input from the ipsilateral auditory nerve. Elimination of activity in the auditory nerve on one side of the brain has been shown to alter a number of properties of NM neurons. For example, after a couple of days, a portion of the neurons in NM die and the rest shrink in size. Early after the elimination of auditory nerve activity in young chicks, changes in metabolism in NM neurons have been observed. For example, within 1 hour, there is a dramatic decrease in protein synthesis by NM neurons on the ipsilateral side of the brain. Such changes in NM neurons structure and function, however, are not observed after elimination of auditory nerve activity in adult birds. The proposed experiments investigate the signals involved in the regulation of both the electrical activity and metabolic activity of NM neurons. These experiments will be carried out on both young (1-2 week old) and adult (1 year old) chickens. Regulation of electrical activity is investigated first by analyzing the anatomical distribution of different classes of excitatory amino acid receptors. The physiological effects of excitatory amino acids are then assessed by application of specific agonists and antagonists while recording intracellularly from NM neurons in an in vitro brain slice preparation. Metabolic regulation is investigated by assessing changes in protein synthesis in the in vitro slice preparation after various treatments. Unilateral stimulation of the auditory nerve in vitro has been shown to produce similar changes in protein synthesis as those observed in vivo. Application of specific agonists and antagonists will assess the relative roles of different types of excitatory amino acid receptors and second messenger systems in transneuronal regulation of brain stem auditory system, 2) an understanding of the signals responsible for the regulation of neuronal metabolism in this system and 3) an understanding of age-related differences which may account for the age- dependence in the sensitivity of neurons to alterations of afferent activity.