Brain Damage and Recovery of Function in the Adult System

描述(申请人提供)：我们的长期目标是确定如何帮助成年脑损伤受害者恢复因中风或其他疾病而受损的大脑区域的功能。为此，这项研究的目标是确定成人大脑损伤后功能恢复的机制。本提案建立在两个概念上互补的意见的基础上。我们观察到，当一只雄性环鸽与一只雌性环鸽在一起时，成年雄性环鸽双侧下丘脑损伤后复杂的求偶行为(巢穴)的恢复是容易的。其次，电解损毁成年大鼠下丘脑后，损毁后2~3个月，对雌巢COO刺激反应正常、行为恢复正常的单位，损毁部位可同时检测到新生神经元。这些观察结果提出了对被广泛接受的功能恢复原则的另一种解释。恢复可能不仅由现有的、未受损的神经元介导，也可能由损伤诱导的新神经元重新加入重组网络而介导。我们通过阻断神经发生并观察其对恢复的影响(目标I)和确定新神经元是否具有生物学功能，即它们是否整合到巢COO行为网络中来检验损伤诱导的新神经元参与了生理活动和巢COO行为的恢复的假设。这将通过测量与巢COO行为相关的内分泌输出，以及通过使用束追踪和神经元标记的联合免疫组织化学(AIM II)来确定新神经元的轴突连接来进行测试。综上所述，本提案试图确定病变诱导的神经发生在成熟鸽脑功能恢复的背景下所起的作用。

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.