Neural Basis of Behavioral Flexibility

描述（由申请人提供）：行为不仅由刺激决定，而且由那些行为生成网络的内部状态决定，这些行为生成网络起感觉运动整合器的作用。网络状态的一个重要类型是依赖于最近经历的记忆的经验依赖性状态。因此，为了产生反应，网络整合了当前刺激和最近经历的记忆，这些记忆被表达为网络状态。我们建议研究经验依赖的状态是如何产生的，表达，并与刺激，冲击网络整合。为了达到这个目的，我们将使用一种充分表征的制剂，它能产生摄食和排泄反应。我们将使用多学科的方法，结合电生理学，生物化学和细胞生物学技术。重复刺激刺激诱发消化反应的输入建立了一种网络状态，这种网络状态表现在重复启动中，即，反应的自发性逐渐增加。重要的是，在重复刺激排泄输入之后，观察到任务转换成本，即，刺激摄食输入现在激发摄食反应而不是摄食反应。同一个网络状态有两种不同的表现形式，这一事实使得网络状态和网络连通性的功能分离成为可能。基于一系列最近的研究结果，我们提出，EN刺激依赖的网络状态不是通过招募一组单一的专门的神经元来实现的，而是由于几个神经元的兴奋性的平行肽能调制而出现的，这些神经元在表达网络状态的各种表现中起着关键作用。然而，网络状态并不是反应的唯一决定因素。我们提出，网络在不同状态下产生的反应的特异性不仅取决于网络的瞬时状态，而且还取决于网络内神经元连接的特征。最后，我们建议网络状态的助记成分，即，神经元兴奋性的持续改变是由特定第二信使系统的肽能激活介导的，我们打算测试其作用。在帕金森病、自闭症儿童中观察到各种形式的运动开始和重复的病理学，并且也是由于脑损伤而诱发的。因此，我们希望了解我们提出研究的现象的机制可能是对这些疾病的一个新的视角。 公共卫生相关性：我们建议研究行为转换和稳定性的神经基础。这两个过程在儿童自闭症和帕金森病中被破坏。这些研究可能会导致对这些疾病中行为缺陷性质的新见解。

DESCRIPTION (provided by applicant): Behavior is determined not only by stimuli but also by internal states of those behavior generating networks that function as sensory motor-integrators. An important type of network state is an experience-dependent state that relies on the memory of recent experiences. Consequently, to generate responses, networks integrate both current stimuli and memories of recent experiences that are expressed as network states. We propose to study how experience dependent states are generated, expressed, and integrated with stimuli that impinge on the network. Towards this purpose, we will use a well characterized preparation that generates ingestive and egestive responses. We will use a multidisciplinary approach that combines electrophysiological, biochemical and cell-biological techniques. Repetitive stimulation of an input that elicits egestive responses establishes a network state that is manifested in repetition priming, i.e., a progressive increase of egestiveness of the response. Importantly, in the aftermath of repetitive stimulation of egestive inputs, a task switch cost is observed, i.e., stimulation of an ingestive input now elicits egestive rather than ingestive responses. The fact that the same network state has two different manifestations has made it possible to dissociate the functions of network states and network connectivity. Based on a series of recent findings, we propose that the EN- stimulation dependent network state is not implemented through recruitment of a singular set of specialized neurons but instead emerges as a result of the parallel peptidergic modulation of the excitability of several neurons that play a critical role in expressing various manifestations of network states. However, network states are not the sole determinant of responses. We propose that the specificity of responses that networks generate in different states depends not only on the momentary state of the network but also on the characteristics of neuronal connections within the network. Finally, we suggest that the mnemonic component of network states, i.e., persistent modification of neuronal excitability is mediated by peptidergic activation of specific second messenger systems whose role we propose to test. Various forms of pathology of initiation and repetition of movements are observed in Parkinsons disease, autistic children, and are also induced as a result of brain lesions. Thus, it may be hoped that understanding the mechanisms of the phenomena that we propose to study may a novel perspective on these disorders. PUBLIC HEALTH RELEVANCE: We propose to study the neural basis of behavior switching and stability. These two processes are disrupted in childhood autism and Parkinson's disease. These studies may lead to novel insights into the nature of the behavioral deficits in these diseases.