Information processing in the nucleus accumbens

描述（由申请人提供）：丘脑核是一个大脑区域，在处理奖励信息和选择适合于上下文的行为方面起着重要作用。有人提出，背景引导伏隔核反应选择的一种机制是通过突触相互作用，该相互作用被描述为门控机制;海马输入被认为是其他输入驱动伏隔核动作电位放电所必需的。虽然门控假说已经得到了一些研究的进一步支持，新的数据表明，在需要选择行为的时期，脑桥核可以脱离海马的输入，并跟随前额叶的活动。我们提出，丘脑核可以表现为一个开关板，反应选择发生在多个传入之间的相互作用。在这里，我们将测试是否整合的信息，在nucleus的决策和选择适当的行为反应，以一个给定的情况下，使用多通道录音（同时从前额叶皮层，海马和nucleus的）在两个不同的操作性任务是至关重要的。此外，我们将探讨这些相互作用的突触机制，在体内细胞内记录和全细胞记录在海马切片，旨在测试是否强大的前额叶传入激活可以减弱海马传入的影响，以及这种相互作用是否依赖于当地的GABA或多巴胺。揭开负责反应选择的细胞和突触过程，将促进我们对这一关键功能的理解，并为包括精神分裂症在内的神经精神疾病的病理生理学的新观点铺平道路，并可能最终寻求新的治疗方法。 公共卫生相关性：这个项目将测试信息在核神经元的整合是否是决策和选择适当的行为反应的一个给定的情况下至关重要。特别是，我们将评估前额叶皮层的活动影响海马体对丘脑核电活动的影响以及依赖于它的行为的方式。在这个关键的大脑区域中，这种信息的整合对于理解决策和反应选择非常重要，了解其机制将有助于我们开发更好的模型来解释精神障碍。

DESCRIPTION (provided by applicant): The nucleus accumbens is a brain region with an important role in processing reward information and the selection of behaviors appropriate to the context. It has been proposed that one mechanism by which context guides response selection in the nucleus accumbens is via a synaptic interaction that has been characterized as a gating mechanism; hippocampal inputs are believed to be necessary for other inputs to drive action potential firing in the nucleus accumbens. Although the gating hypothesis has received further support from several studies, novel data indicate that the nucleus accumbens could disengage from its hippocampal inputs and follow prefrontal activity during epochs in which selection of a behavior is required. We proposed that the nucleus accumbens can behave a switchboard where response selection takes place by the interactions among multiple afferents. Here we will test whether the integration of information in the nucleus accumbens is critical for decision-making and selection of the appropriate behavioral response to a given context using multichannel recordings (simultaneously from the prefrontal cortex, hippocampus and nucleus accumbens) in two different operant tasks. Furthermore, we will explore the synaptic mechanisms underlying these interactions with in vivo intracellular recordings and whole cell recordings in accumbens slices, aimed at testing whether strong prefrontal afferent activation can attenuate the impact of hippocampal afferents and whether this interaction is dependent on local GABA or dopamine. Unveiling the cellular and synaptic processes responsible for response selection in the nucleus accumbens would advance our understanding of this critical function and pave the way to novel views on the pathophysiology of neuropsychiatric disorders, including schizophrenia, and perhaps eventually seek novel therapeutic approaches. PUBLIC HEALTH RELEVANCE: This project will test whether the integration of information in the nucleus accumbens is critical for decision-making and selection of the appropriate behavioral response to a given context. In particular, we will assess the manner activity in the prefrontal cortex affects the influence exerted by the hippocampus on nucleus accumbens electrical activity and the behaviors that depend on it. Such integration of information in this critical brain region is important for understanding decision making and response selection and gaining an understanding of its mechanism will helps us develop better models to explain mental disorders.