Brain Damage and Recovery of Function in the Adult System

描述（由申请人提供）：我们的长期目标是确定如何帮助脑损伤的成年受害者恢复因中风或其他疾病受损的大脑区域的功能。为此，本研究的目的是确定成人大脑损伤后功能恢复的机制。本建议建立在两个概念上互补的意见基础上。我们观察到，成年雄环鸽在双侧下丘脑损伤后的复杂求偶行为（巢内咕咕叫）在雄环鸽与雌环鸽共同生活时得到了促进。其次，在成年下丘脑电解损伤后，在损伤部位检测到新生神经元，同时在损伤部位恢复，在损伤后2-3个月，对雌性巢coo刺激有正常放电反应的单位在损伤部位恢复。这些观察结果为广泛接受的功能恢复原理提供了另一种解释。恢复可能不仅是由现有的、未受损的神经元介导的，也可能是由损伤诱导的新神经元招募到重组网络中。我们通过阻断神经发生并观察其对恢复的影响（Aim I），以及确定新神经元是否具有生物学功能，即它们是否整合到巢巢行为网络中，来验证损伤诱导的新神经元参与生理活动和巢巢行为恢复的假设。这将通过测量与巢巢行为相关的内分泌输出，并通过结合免疫组织化学的束示踪和神经元标志物来确定新神经元的轴突连接来进行测试（Aim II）。总之，目前的建议旨在确定损伤诱导的神经发生在成熟鸽子大脑功能恢复的背景下的作用。

DESCRIPTION (provided by applicant): Our long-term goal is to determine how to help adult victims of brain injury recover the function of brain areas damaged by stroke or other afflictions. To that end, the goal of this study is to determine the mechanisms that underlie the recovery of function after damage to the adult brain. The present proposal builds upon two conceptually complementary observations. We have observed that the recovery of complex courtship behavior (the nest coo) after bilateral hypothalamic lesion in the adult male ring dove is facilitated when a male ring dove is housed with a female. Secondly, after electrolytic lesions of the adult hypothalamus, newborn neurons were detected at the lesion site concurrent with recovery at the lesion site of units exhibiting normal firing responses to female nest coo stimulation and behavioral recovery 2-3 months after lesion. These observations suggest an alternative explanation to the widely accepted principle of recovery of function. Recovery might be mediated not only by existing, undamaged neurons, but also by lesion-induced new neurons recruited into the network of reorganization. We test the hypothesis that lesion-induced new neurons are involved in the recovery of physiological activity and nest coo behavior by blocking neurogenesis and observing the effects on recovery (Aim I) and the determining whether the new neurons are biologically functional, namely, whether they are integrated into the network of nest coo behavior. This will be tested by measuring endocrine output associated with the nest coo behavior, and by determining axonal connections of new neurons using combined immunohistochemistry of tract tracing and neuronal markers (Aim II). In sum, the present proposal seeks to determine the role of lesion-induced neurogenesis in the context of the recovery of function in the mature dove brain.