Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons.
Chaudhury D, Walsh JJ, Friedman AK, Juarez B, Ku SM, Koo JW, Ferguson D, Tsai HC, Pomeranz L, Christoffel DJ, Nectow AR, Ekstrand M, Domingos A, Mazei-Robison MS, Mouzon E, Lobo MK, Neve RL, Friedman JM, Russo SJ, Deisseroth K, Nestler EJ, Han MH.
Nature. 2013 Jan 24;493(7433):532-6. doi: 10.1038/nature11713. Epub 2012 Dec 12.
Social-defeat stressに暴露することによって、うつ病ライクな行動が誘発されるがそのときの腹側被蓋野(VTA)のドーパミンニューロン(DA)の活動を記録するとfiring rateは「上昇」し、bursticな放電が増える(Krishnan et al.,Cell,2008; Cao et al.,J.Neurosci.,2010)。このDAの活動上昇とdepression-like behaviorの発現との関係を直接的に調べるためにoptogeneticsの技術を使って調べた。
その結果、
・DAだけを選択的に光刺激(Phasic刺激が有効でありtonicな刺激は有効でない)すると、depression-like behaviorが誘発される(ストレスを受けているとき、その後でも)。
・この刺激効果はcontext-specific(ストレスを受けていないマウスでは影響なし) 。
・ストレス暴露によって、depression-like behaviorが起きるマウス(susceptible)とそうでないマウス(resilient)に分類できるが、resilientマウスであってもVTAの光刺激によってsusceptibleマウスとなる。
さらに、逆行性トレーサーを使ってNAcに投射しているVTA DAニューロンとmPFC投射ニューロンに分けて調べており、上記のようなsocial defeat stressに対する感受性を調節しているようなpathwayはVTA-NAc pathwayの方であるとしている。
おもしろいと思ったのは、
DAニューロンの活動が上がるとうつ病様行動が誘発されるといういわゆる直感に反したような結果であるということと、こういった影響がストレスを受けたという記憶や経験に基づいて起きるということ。
それとNAcのcholinergic interneuronの選択的ブロックでうつ病様行動が誘発されるというGreengardらの研究との関連も気になっています。NAc内のどのようなタイプの細胞がドーパミンや他の入力と相まってmotivated behaviorを駆動しているのか？
そもそも今回のパラダイムでマウスはストレスと感じているのか？ストレス暴露後のsocial interaction testでcontrolマウスのsocial interactionが上がっているのはなぜなのか？
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関連論文
Dopamine neurons modulate neural encoding and expression of depression-related behaviour.
Tye KM, Mirzabekov JJ, Warden MR, Ferenczi EA, Tsai HC, Finkelstein J, Kim SY, Adhikari A, Thompson KR, Andalman AS, Gunaydin LA, Witten IB, Deisseroth K.
Nature. 2013 Jan 24;493(7433):537-41. doi: 10.1038/nature11740. Epub 2012 Dec 12.
Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.
Lemos JC, Wanat MJ, Smith JS, Reyes BA, Hollon NG, Van Bockstaele EJ, Chavkin C, Phillips PE.
Nature. 2012 Oct 18;490(7420):402-6. doi: 10.1038/nature11436. Epub 2012 Sep 19.
A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge.
Warden MR, Selimbeyoglu A, Mirzabekov JJ, Lo M, Thompson KR, Kim SY, Adhikari A, Tye KM, Frank LM, Deisseroth K.
Nature. 2012 Dec 20;492(7429):428-32. doi: 10.1038/nature11617.
2013/01/28
2013/01/28 木村
Human dorsal anterior cingulate cortex neurons mediate ongoing behavioural adaptation.
Sheth SA, Mian MK, Patel SR, Asaad WF, Williams ZM, Dougherty DD, Bush G, Eskandar EN.
Nature. 2012 Aug 9;488(7410):218-21.
The ability to optimize behavioural performance when confronted with continuously evolving environmental demands is a key element of human cognition. The dorsal anterior cingulate cortex (dACC), which lies on the medial surface of the frontal lobes, is important in regulating cognitive control. Hypotheses about its function include guiding reward-based decision making1, monitoring for conflict between competing responses2 and predicting task difficulty3. Precise mechanisms of dACC function remain unknown, however, because of the limited number of human neurophysiological studies. Here we use functional imaging and human single-neuron recordings to show that the firing of individual dACC neurons encodes current and recent cognitive load. We demonstrate that the modulation of current dACC activity by previous activity produces a behavioural adaptation that accelerates reactions to cues of similar difficulty to previous ones, and retards reactions to cues of different difficulty. Furthermore, this conflict adaptation, or Gratton effect2, 4, is abolished after surgically targeted ablation of the dACC. Our results demonstrate that the dACC provides a continuously updated prediction of expected cognitive demand to optimize future behavioural responses. In situations with stable cognitive demands, this signal promotes efficiency by hastening responses, but in situations with changing demands it engenders accuracy by delaying responses.
Sheth SA, Mian MK, Patel SR, Asaad WF, Williams ZM, Dougherty DD, Bush G, Eskandar EN.
Nature. 2012 Aug 9;488(7410):218-21.
The ability to optimize behavioural performance when confronted with continuously evolving environmental demands is a key element of human cognition. The dorsal anterior cingulate cortex (dACC), which lies on the medial surface of the frontal lobes, is important in regulating cognitive control. Hypotheses about its function include guiding reward-based decision making1, monitoring for conflict between competing responses2 and predicting task difficulty3. Precise mechanisms of dACC function remain unknown, however, because of the limited number of human neurophysiological studies. Here we use functional imaging and human single-neuron recordings to show that the firing of individual dACC neurons encodes current and recent cognitive load. We demonstrate that the modulation of current dACC activity by previous activity produces a behavioural adaptation that accelerates reactions to cues of similar difficulty to previous ones, and retards reactions to cues of different difficulty. Furthermore, this conflict adaptation, or Gratton effect2, 4, is abolished after surgically targeted ablation of the dACC. Our results demonstrate that the dACC provides a continuously updated prediction of expected cognitive demand to optimize future behavioural responses. In situations with stable cognitive demands, this signal promotes efficiency by hastening responses, but in situations with changing demands it engenders accuracy by delaying responses.
2013/01/22 榎本
Neuronal reference frames for social decisions in primate frontal cortex.
Chang SW, Gariepy JF, Platt ML.
Nat Neurosci. 2012 Dec 23.
紹介記事
http://www.nature.com/news/monkey-brain-area-keeps-count-of-kindnesses-1.12116
http://phenomena.nationalgeographic.com/2012/12/23/social-brain-one-neuron-at-a-time/
Chang SW, Gariepy JF, Platt ML.
Nat Neurosci. 2012 Dec 23.
紹介記事
http://www.nature.com/news/monkey-brain-area-keeps-count-of-kindnesses-1.12116
http://phenomena.nationalgeographic.com/2012/12/23/social-brain-one-neuron-at-a-time/
2013/01/22 野々村
The Role of the Anterior Cingulate Cortex in Choices based on Reward Value and Reward Contingency.
Chudasama Y, Daniels TE, Gorrin DP, Rhodes SE, Rudebeck PH, Murray EA.
Cereb Cortex. 2012 Sep 3
Chudasama Y, Daniels TE, Gorrin DP, Rhodes SE, Rudebeck PH, Murray EA.
Cereb Cortex. 2012 Sep 3
2013/01/15
2013/01/15 春野
How the opinion of others affects our valuation of objects.
Campbell-Meiklejohn DK, Bach DR, Roepstorff A, Dolan RJ, Frith CD.
Curr Biol. 2010 Jul 13;20(13):1165-70.
2013/01/15 田中
Clan mentality: evidence that the medial prefrontal cortex responds to close others.
Krienen FM, Tu PC, Buckner RL.
J Neurosci. 2010 Oct 13;30(41):13906-15.
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