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Dopamine neurons modulate neural encoding and expression of depression-related behaviour

机译:多巴胺神经元调节抑郁相关行为的神经编码和表达

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摘要

Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia1. Dopamine neurons involved in reward and motivation are among many neural populations that have been hypothesized to be relevant, and certain antidepressant treatments, including medications and brain stimulation therapies, can influence the complex dopamine system. Until now it has not been possible to test this hypothesis directly, even in animal models, as existing therapeutic interventions are unable to specifically target dopamine neurons. Here we investigated directly the causal contributions of defined dopamine neurons to multidimensional depression-like phenotypes induced by chronic mild stress, by integrating behavioural, pharmacological, optogenetic and electrophysiological methods in freely moving rodents. We found that bidirectional control (inhibition or excitation) of specified midbrain dopamine neurons immediately and bidirectionally modulates (induces or relieves) multiple independent depression symptoms caused by chronic stress. By probing the circuit implementation of these effects, we observed that optogenetic recruitment of these dopamine neurons potently alters the neural encoding of depression-related behaviours in the downstream nucleus accum-bens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry.
机译:重度抑郁症的特征在于多种多样的使人衰弱的症状,包括绝望和快感不足1。参与奖励和动机的多巴胺神经元是许多被认为是相关的神经种群,某些抗抑郁疗法,包括药物和脑刺激疗法,可能会影响复杂的多巴胺系统。到目前为止,由于现有的治疗方法无法特异性针对多巴胺神经元,因此即使在动物模型中也无法直接检验该假设。在这里,我们通过将行为,药理,光遗传学和电生理学方法整合到自由移动的啮齿动物中,直接研究了确定的多巴胺神经元对慢性轻度应激诱导的多维抑郁样表型的因果贡献。我们发现指定的中脑多巴胺神经元的双向控制(抑制或激发)立即并双向调节(诱导或缓解)由慢性应激引起的多种独立的抑郁症状。通过探究这些效应的电路实现,我们观察到这些多巴胺神经元的光遗传募集有效地改变了自由移动啮齿动物下游伏隔核中与抑郁相关的行为的神经编码,表明影响抑郁症状的过程可能涉及改变。边缘电路中动作的神经编码。

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  • 来源
    《Nature》 |2013年第7433期|537-541|共5页
  • 作者单位

    Picower Institute for Learning and Memory, Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA,Department of Bioengineering, Stanford University, Stanford, California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA,Neurosciences Program, Stanford University, Stanford California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA,Neurosciences Program, Stanford University, Stanford California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA,Neurosciences Program, Stanford University, Stanford California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA;

    Department of Bioengineering, Stanford University, Stanford, California 94305, USA,Neurosciences Program, Stanford University, Stanford California 94305, USA,Department of Psychiatry and Behavioral Sciences, Stanford University,Stanford, California 94305, USA,Howard Hughes Medical Institute, Stanford University, Stanford California 94305, USA,CNC Program, Stanford University, Stanford, California 94305, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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