Interacting neural ensembles in orbitofrontal cortex for social and feeding behaviour
Interacting neural ensembles in orbitofrontal cortex for social and feeding behaviour
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DOI：
10.1038/s41586-018-0866-8
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发表时间：
2019-01-31
期刊：
影响因子：
64.8
通讯作者：
Deisseroth, Karl
中科院分区：
文献类型：
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作者：
Jennings, Joshua H.;Kim, Christina K.;Deisseroth, Karl
分类上不同的基本驱动力（例如，社交行为与进食行为（1-3））可以相互施加强有力的影响;这种相互作用可能具有重要的适应性后果（例如在社会等级背景下对进食的适当调节），并可能变得适应不良（例如在涉及厌食症的临床环境中）。众所周知，调节自然和适应性热量摄入的神经系统，以及调节社会行为的神经系统，涉及相关的回路（4-7），但这些驱动裁决的因果回路机制尚不清楚。在这里，我们研究了眶额皮质中细胞分辨体验特异性神经元群体行为的因果作用，眶额皮质是一个主要的奖励处理中心，包含不同的活动特异性神经元群体，这些神经元群体对热量摄入（8-13）和社会刺激（14，15）的各个方面有不同的反应。我们将遗传编码的活动成像与多个单独定义的细胞的光遗传学控制方法的开发和应用相结合，以在奖励体验（热量消耗和社会互动）期间以真实的时间在单细胞水平上光学监测和操纵许多眶额皮层神经元的活动。我们确定了眶额皮质内的不同群体，这些群体选择性地对热量奖励或社会刺激做出反应，并发现个别指定的天然摄食反应神经元的活动与增加的摄食行为有因果关系;这种效应是选择性的，因为相比之下，自然社会反应神经元的单细胞分辨激活抑制进食，对摄食和社会刺激都没有反应的神经元的激活并不改变摄食行为。这些结果揭示了眶额皮质内存在有效的细胞水平子网络，这些子网络可以精确地参与双向控制受例如社会影响的进食行为。
Categorically distinct basic drives (for example, for social versus feeding behaviour(1-3)) can exert potent influences on each other; such interactions are likely to have important adaptive consequences (such as appropriate regulation of feeding in the context of social hierarchies) and can become maladaptive (such as in clinical settings involving anorexia). It is known that neural systems regulating natural and adaptive caloric intake, and those regulating social behaviours, involve related circuitry(4-7), but the causal circuit mechanisms of these drive adjudications are not clear. Here we investigate the causal role in behaviour of cellular-resolution experience-specific neuronal populations in the orbitofrontal cortex, a major reward-processing hub that contains diverse activity-specific neuronal populations that respond differentially to various aspects of caloric intake(8-13) and social stimuli(14,15). We coupled genetically encoded activity imaging with the development and application of methods for optogenetic control of multiple individually defined cells, to both optically monitor and manipulate the activity of many orbitofrontal cortex neurons at the single-cell level in real time during rewarding experiences (caloric consumption and social interaction). We identified distinct populations within the orbitofrontal cortex that selectively responded to either caloric rewards or social stimuli, and found that activity of individually specified naturally feeding-responsive neurons was causally linked to increased feeding behaviour; this effect was selective as, by contrast, single-cell resolution activation of naturally social-responsive neurons inhibited feeding, and activation of neurons responsive to neither feeding nor social stimuli did not alter feeding behaviour. These results reveal the presence of potent cellular-level subnetworks within the orbitofrontal cortex that can be precisely engaged to bidirectionally control feeding behaviours subject to, for example, social influences.