Information processing in the nucleus accumbens

描述（由申请人提供）：伏隔核是大脑的一个区域，在处理奖励信息和选择适合情境的行为方面起着重要作用。有人提出，情境引导伏隔核反应选择的一种机制是通过一种被描述为门控机制的突触相互作用；海马输入被认为是其他输入驱动伏隔核动作电位放电的必要条件。尽管门控假说得到了几项研究的进一步支持，但新的数据表明，在需要选择行为的时期，伏隔核可能脱离海马体输入，跟随前额叶活动。我们提出伏隔核可以作为一个交换机，通过多个传入事件之间的相互作用进行反应选择。在这里，我们将通过在两种不同的操作任务中使用多通道录音（同时来自前额皮质、海马和伏隔核）来测试伏隔核的信息整合是否对给定环境下的决策和选择适当的行为反应至关重要。此外，我们将通过体内细胞内记录和伏隔核切片的全细胞记录来探索这些相互作用背后的突触机制，旨在测试强烈的前额叶传入事件激活是否会减弱海马传入事件的影响，以及这种相互作用是否依赖于局部GABA或多巴胺。揭示伏隔核中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，并为神经精神疾病（包括精神分裂症）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。

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.