Dopamine neurons modulate neural encoding and expression of depression-related behaviour.
Dopamine neurons modulate neural encoding and expression of depression-related behaviour.
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作者：
重度抑郁症的特征是各种各样的衰弱症状，包括绝望和快感缺乏。参与奖励和动机的多巴胺神经元是许多被假设为相关的神经群体之一，某些抗抑郁治疗，包括药物和脑刺激疗法，可以影响复杂的多巴胺系统。到目前为止，即使在动物模型中也无法直接验证这一假设，因为现有的治疗干预措施无法特异性靶向多巴胺神经元。在这里，我们直接调查的因果关系的贡献定义多巴胺神经元的多维抑郁症样表型诱导的慢性轻度压力，通过整合行为，药理学，光遗传学和电生理学方法在自由移动的啮齿动物。我们发现，指定的中脑多巴胺神经元的双向控制（抑制或兴奋）立即双向调制（诱导或缓解）慢性应激引起的多种独立的抑郁症状。通过探测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学募集有效地改变了自由移动啮齿动物下游丘脑核中抑郁相关行为的神经编码，这表明影响抑郁症状的过程可能涉及改变边缘系统回路中的神经编码行为。
Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia. 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 accumbens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry.
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神经元型特异性信号，用于腹侧对段区域的奖励和惩罚。
影响因子：
64.8
作者：
Cohen, Jeremiah Y.;Haesler, Sebastian;Vong, Linh;Lowell, Bradford B.;Uchida, Naoshige
通讯作者：
Uchida, Naoshige
DOI：
10.1523/jneurosci.5952-11.2012
发表时间：
2012-03-21
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Tanaka K;Furuyashiki T;Kitaoka S;Senzai Y;Imoto Y;Segi-Nishida E;Deguchi Y;Breyer RM;Breyer MD;Narumiya S
通讯作者：
Narumiya S
影响因子：
2.9
作者：
FREEMAN, AS;BUNNEY, BS
通讯作者：
BUNNEY, BS
影响因子：
16.2
作者：
Mayberg, HS;Lozano, AM;Kennedy, SH
通讯作者：
Kennedy, SH
影响因子：
4.7
作者：
Ikemoto, S;Wise, RA
通讯作者：
Wise, RA