Cell Survival in a Neural Circuit for Learning

描述（由申请人提供）：像人类一样，鸣禽在早期发育的敏感时期学习其物种用于交流的声音。在许多鸣禽物种中，只有雄性会唱歌，这种行为性别差异的一个显著后果是，成年雄性大脑中控制鸣叫的区域很突出，而成年雌性大脑中控制鸣叫的区域则变小（或缺失）。在斑胸草雀中，一些声音控制区域最初在两性中都有发育。然而，在鸣叫学习的幼年阶段，这些区域在雌性中表现出大量的神经元死亡，而在雄性中表现出很少的神经元死亡。我们的工作假设是，鸣叫学习的质量和鸣叫区域的形态发展受到幼鸟练习声音模式的频率的影响。使用依赖机制在运动学习、神经生长和可塑性中的作用在包括人类在内的其他动物中有充分的先例。然而，使用依赖机制在声乐学习（人类或鸣禽）中的作用从未被评估过，部分原因是很难衡量一种自愿的行为，这种行为在发展过程中发生在很高的水平。然而，通过使用事件触发记录系统（允许对单个鸟的发声输出进行连续监测），我们已经表明，正在学习唱歌的幼鸟的每日鸣叫量明显高于成年鸟。幼鸟鸣叫的个体差异也最大，幼鸟鸣叫多的鸟类成年后鸣叫质量更高。因此，鸣禽的发声学习似乎涉及一个“实践驱动”的组成部分，它可能与影响神经发育的成熟因素相互作用，并决定成年发声模式的质量。在这种情况下，我们将研究几个基因产物，以建立唱歌与以下因素之间的联系：1)练习效果的储存，2)驱动歌曲区域增长的机制，以及3)影响青少年歌曲排练的动机系统。我们将在斑胸草雀身上研究的所有基因系统都显示出与人类的高度同源性，所以我们对它们在鸣禽中的作用的了解可能对人类大脑发育和声乐学习具有功能意义。

DESCRIPTION (provided by applicant): Like humans, songbirds learn the sounds used by their species to communicate during a sensitive period of early development. In many songbird species only males learn to sing and a striking consequence of this behavioral sex difference is that the brain regions for song control are prominent in adult males and diminished in size (or absent) in adult females. In the zebra finch, some vocal control regions initially develop in both sexes. However, during the juvenile phase of song learning these regions show substantial neuron death in females, and growth with little neuron death in males. Our working hypothesis is that the quality of song learning and the morphological development of song regions are influenced by how often juvenile birds practice their vocal pattern. A role for use-dependent mechanisms in motor learning and neural growth and plasticity has ample precedent in other animals, including humans. However, the contribution of use-dependent mechanisms in vocal learning (human or songbird) has never been evaluated, partly because of the difficulty of measuring a behavior that is voluntary and that occurs at high levels over the course of development. However, with the use of an event-triggered recording system (which allows continuous monitoring of the vocal output of individual birds), we have shown that daily song production is significantly greater in juvenile birds that are learning to sing than in adults. Individual differences in song production are also greatest in juveniles, and birds that sing more as juveniles have a higher quality song as adults. Thus, songbird vocal learning appears to involve a 'practice-driven' component, which may interact with maturational factors to influence neural development and determine the quality of the adult vocal pattern. Several gene products will be examined in this context to establish links between singing and 1.) storage of the effects of practice, 2.) mechanisms that drive the growth of song regions, and 3.) motivational systems that influence rehearsal of song by juveniles. All of the gene systems that we will study in zebra finches show a high degree of homology to their human counterparts, so what we learn about their role in songbirds may have functional implications for human brain development and vocal learning.