Chemical Reward Systems for Embodied Cultured Networks

描述(由申请人提供)： 成瘾物质通过激活奖励机制来控制大脑的自然学习机制，奖励机制加强了与吸毒相关的行为。但在行为、大脑系统和细胞药理学层面上，人们对这些机制了解多少。然而，在我们对细胞可塑性和行为之间的动态关系的理解上有很大的差距。我们将使用多电极阵列上培养的神经元网络，结合长时间刺激和记录，在微观和介观尺度上探索与奖励相关的神经可塑性。奖赏相关的神经调节剂将应用于网络，在神经控制的动物范式的背景下，研究它们对生理和形态可塑性的影响，在该范式中，网络活动控制模拟动物的行为。延时成像，使用双光子和广域视频显微镜，将使我们能够详细观察与学习、记忆和成瘾相关的细胞和网络水平的形态动力学。通过创造一个体外奖励系统，我们可以比在动物或人类身上更详细地观察和操纵与奖励相关的可塑性。通过将培养的神经网络具体化，我们可以将神经可塑性的体外研究带到行为水平，并增强它们与体内成瘾机制的相关性。

DESCRIPTION (provided by applicant): Addictive substances take control of the brain's natural learning mechanisms, by activating reward mechanisms that reinforce behaviors associated with drug taking. But how much is known about these mechanisms at the levels of behavior, of brain systems, and of cellular pharmacology. However, there is a large gap in our understanding of the dynamic relationships between cellular plasticity and behavior. We will explore reward-related neural plasticity at the microscopic and mesoscopic scale using neuronal networks cultured on multi-electrode arrays with tong-term stimulation and recording. Reward-related neuromodulators will be applied to the networks to study their influence on physiological and morphological plasticity, in the context of the Neurally-Controlled Animal paradigm, in which network activity controls the behavior of a simulated animal. Time-lapse imaging, using both 2-photon and wide-field videomicroscopy, will allow us to observe in detail cellular and network-level morphological dynamics related to learning, memory, and addiction. By creating an in-vitro reward system, we can observe and manipulate reward related plasticity in much greater detail than possible in animals or people. By embodying the cultured networks, we can bring in-vitro studies of neural plasticity to the behavioral level, and enhance their relevance to addiction mechanisms in vivo.