Neural Basis of Behavioral Flexibility

行为灵活性的神经基础

• 批准号: 8208106
• 负责人: ELIZABETH C CROPPER
• 金额: $ 36.02万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8208106
• 关键词: Accounting; Activity Cycles; Animals; Aplysia; Autistic Disorder; Behavior; Behavioral; Biochemical; Biological; Brain; Cells; Characteristics; Childhood; Disease; Elements; Esophageal; Event; Interneurons; Lead; Lesion; Mediating; Memory; Modification; Motor; Movement; Nature; Nerve; Neurons; Neuropeptides; Neurotransmitters; Output; Parkinson Disease; Pathology; Play; Preparation; Process; Role; Second Messenger Systems; Sensory; Series; Signal Transduction Pathway; Specificity; Stimulus; System; Techniques; Testing; autistic children; base; central pattern generator; cost; experience; feeding; flexibility; insight; interdisciplinary approach; interest; neuronal excitability; novel; programs; public health relevance; relating to nervous system; response

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.

描述（由申请人提供）：行为不仅由刺激决定，还由那些充当感觉运动积分器的行为生成网络的内部状态决定。网络状态的一种重要类型是依赖于最近经历的记忆的经验依赖状态。因此，为了产生响应，网络整合了当前的刺激和最近经历的记忆，并以网络状态的形式表达。我们建议研究经验依赖状态是如何生成、表达以及如何与影响网络的刺激相结合的。为了实现这一目的，我们将使用一种特征明确的制剂来产生摄入和消化反应。我们将采用结合电生理学、生物化学和细胞生物学技术的多学科方法。引起食欲反应的输入的重复刺激建立了一种网络状态，该状态表现为重复启动，即反应的食欲逐渐增加。重要的是，在重复刺激食欲输入之后，观察到任务转换成本，即，摄入输入的刺激现在引起食欲反应而不是摄入反应。同一网络状态有两种不同的表现形式，使得网络状态和网络连通性的功能分离成为可能。基于一系列最近的发现，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神经元来实现的，而是作为多个神经元兴奋性的并行肽能调节的结果而出现，这些神经元在表达网络状态的各种表现中发挥着关键作用。然而，网络状态并不是响应的唯一决定因素。我们提出，网络在不同状态下生成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，我们建议测试其作用。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，并且也由于脑损伤而诱发。因此，希望了解我们打算研究的现象的机制可能会为这些疾病提供新的视角。 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。这些研究可能会对这些疾病的行为缺陷的本质产生新的见解。