Optogenetic investigations of motivational circuits in rats and mice

先前的药理学研究表明中缝中区（MR）参与情绪调节。具体来说，大鼠将自我给药GABA受体激动剂、AMPA受体拮抗剂和NMDA受体拮抗剂进入中缝正中区（MR）。然而，在MR中有不同种类的神经血清素能、谷氨酸能和GABAergicin，目前还不清楚这些种类在奖励中是如何发挥作用的。为了解决这个问题，本研究利用光遗传学选择性地激发或抑制特定的MR神经元群。野生型C57小鼠在MR中接受编码halorhodopsin （NpHR）的病毒载体，并学会了自我施加光刺激，这表明MR神经元的净抑制是有益的。转基因vGat-Cre小鼠在MR中接受NpHR，导致GABA神经元中选择性表达视蛋白。这些小鼠学会了以比C57小鼠更高的水平自我施加光刺激，这表明GABA神经元的抑制是MR奖励背后的电路的一部分。转基因vGluT3-Cre小鼠在MR中接受通道视紫红质（ChR2），导致视蛋白在谷氨酸神经元中选择性表达。这些小鼠还学会了以比C57小鼠更高的水平自我施加光刺激，这表明谷氨酸神经元的兴奋是MR奖励背后的电路的另一部分。研究表明，MR神经元大量投射到腹侧被盖区（VTA），这是一个已知与奖励和成瘾有关的区域。综上所述，抑制MR GABA神经元可能解除对MR谷氨酸神经元投射到VTA的抑制，从而产生奖励。为了了解成瘾和情绪状态的神经生物学，MR可能是另一个重要的研究区域。

Previous pharmacological research has suggested that the median raphe region (MR) is involved in mood regulation. Specifically, rats will self-administer GABA receptor agonists, AMPA receptor antagonists, and NMDA receptor antagonists into the median raphe region (MR). However, there are diverse populations of neuronsserotonergic, glutamatergic, and GABAergicin the MR, and it is unclear how these populations play roles in reward. To resolve this issue, the present study utilized optogenetics to selectively excite or inhibit particular populations of MR neurons. Wild-type C57 mice received a viral vector encoding halorhodopsin (NpHR) in the MR, and learned to self-administer photostimulation, suggesting that net inhibition of MR neurons is rewarding. Transgenic vGat-Cre mice received NpHR in the MR, resulting in selective expression of the opsin in GABA neurons. These mice learned to self-administer photostimulation at a greater level than C57 mice, suggesting that inhibition of GABA neurons is one part of the circuitry underlying MR reward. Transgenic vGluT3-Cre mice received channelrhodopsin (ChR2) in the MR, resulting in selective expression of the opsin in glutamate neurons. These mice also learned to self-administer photostimulation at a greater level than C57 mice, suggesting that excitation of glutamate neurons is another part of the circuitry underlying MR reward. It has been shown that MR neurons project heavily to the ventral tegmental area (VTA), a region known to be involved in reward and addiction. Taken together, inhibition of MR GABA neurons may disinhibit MR glutamate neurons projecting to the VTA, thereby producing reward. The MR may be another important region to study in order to understand the neurobiology of addiction and mood state.