Neural Basis of Behavioral Flexibility

描述（由申请人提供）：行为不仅由刺激决定，还由这些行为产生网络的内部状态决定，这些网络作为感觉运动集成器发挥作用。一种重要的网络状态是依赖于最近经验的记忆的经验依赖状态。因此，为了产生反应，网络整合了当前的刺激和近期经历的记忆，这些记忆被表达为网络状态。我们建议研究经验依赖状态是如何与冲击网络的刺激产生、表达和整合的。为了达到这个目的，我们将使用一种特性良好的制剂来产生摄取和排泄反应。我们将采用多学科方法，结合电生理、生化和细胞生物学技术。重复刺激引起激发性反应的输入建立了一种网络状态，这种状态表现为重复启动，即反应的激发性逐渐增加。重要的是，在重复刺激摄取性输入之后，观察到任务切换成本，即刺激摄取性输入现在引起摄取性而不是摄取性反应。同样的网络状态有两种不同的表现形式，这使得将网络状态和网络连通性的功能分离开来成为可能。基于最近的一系列发现，我们提出依赖于EN刺激的网络状态不是通过招募一组单一的特化神经元来实现的，而是由于几个神经元的兴奋性的平行肽能调节而出现的，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，网络状态并不是响应的唯一决定因素。我们提出，网络在不同状态下产生的响应的特异性不仅取决于网络的瞬时状态，还取决于网络内神经元连接的特征。最后，我们认为网络状态的助记成分，即神经元兴奋性的持续修饰是由特定第二信使系统的肽能激活介导的，我们建议测试其作用。在帕金森氏症、自闭症儿童中观察到各种形式的运动开始和重复的病理，也可由脑损伤引起。因此，我们希望理解我们提出的研究现象的机制可以为这些疾病提供一个新的视角。

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.