Optogenetic investigations of motivational circuits in rats and mice

以往的药理学研究表明，中缝正中区（MR）参与情绪调节。 具体而言，大鼠将GABA受体激动剂、AMPA受体拮抗剂和NMDA受体拮抗剂自我给药至中缝区域（MR）。然而，在MR中存在着不同的神经元群，包括肾上腺素能神经元、多巴胺能神经元和GABA能神经元，目前还不清楚这些神经元群如何在奖赏中发挥作用。 为了解决这个问题，本研究利用光遗传学来选择性地激发或抑制特定群体的MR神经元。野生型C57小鼠在MR中接受了编码盐视紫红质（NpHR）的病毒载体，并学会了自我管理光刺激，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神经元中视蛋白的选择性表达。这些小鼠比C57小鼠学会了以更高的水平自我管理光刺激，这表明GABA神经元的抑制是MR奖励电路的一部分。转基因vGluT 3-Cre小鼠在MR中接受通道视紫红质（ChR 2），导致视蛋白在谷氨酸神经元中的选择性表达。这些小鼠还学会了以比C57小鼠更高的水平自我管理光刺激，这表明谷氨酸神经元的兴奋是MR奖励电路的另一部分。研究表明，MR神经元大量投射到腹侧被盖区（VTA），这是一个已知与奖赏和成瘾有关的区域。两者合计，抑制MR GABA神经元可以解除抑制MR谷氨酸神经元投射到腹侧被盖区，从而产生奖励。MR可能是另一个重要的研究区域，以了解成瘾和情绪状态的神经生物学。

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.