Neural Basis of Behavioral Flexibility

描述(申请人提供)：行为不仅由刺激决定，也由那些行为产生网络的内部状态决定，这些网络起到感觉运动整合的作用。网络状态的一种重要类型是依赖于经验的状态，它依赖于对最近经验的记忆。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状态是如何产生、表达并与冲击网络的刺激相结合的。为此，我们将使用一种具有良好特性的制剂，以产生摄食和排卵反应。我们将使用结合电生理学、生化和细胞生物学技术的多学科方法。重复刺激一个输入，引起负性反应，建立一种网络状态，这在重复启动中表现出来，即反应的负性逐渐增加。重要的是，在重复刺激负性输入之后，观察到了任务转换成本，即刺激摄取输入现在引起的是排泄反应而不是摄取反应。相同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成为可能。基于最近的一系列发现，我们提出，电刺激依赖的网络状态不是通过招募一组特殊的神经元来实现的，而是由于几个神经元的兴奋性的并行多肽能调制而出现的，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，网络状态并不是响应的唯一决定因素。我们认为，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，还取决于网络中神经元连接的特征。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改变，是由特定的第二信使系统的肽能激活所介导的，我们拟测试其作用。在帕金森氏病、自闭症儿童中可以观察到各种形式的启动和重复运动的病理，也可以由于大脑损伤而诱导。因此，人们可能希望，了解我们提议研究的现象的机制可能会为这些疾病提供一个新的视角。 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氏症中被打乱。这些研究可能会对这些疾病的行为缺陷的性质带来新的见解。

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.