Optogenetic investigations of motivational circuits in rats and mice

前皮质的内侧网络(MN)，包括前臂(PRL)、边缘内(IL)和内侧眶(MO)区，与抑郁症等情感性障碍有关。此外，在啮齿动物中，MN可能包括顶盖顶盖(TT)，因为TT与其他MN结构一样，与PRL、IL和MO相互联系，并可能投射到腹侧纹状体和下丘脑外侧区。对MN谷氨酸能神经元和GABA能神经元在情感过程中的作用知之甚少。我们试图通过小鼠的光遗传和行为程序来了解它们。 将编码视紫红质-2(AAV-ChR2)的腺相关病毒载体导入雄性C57BL/6J小鼠的PRL、IL、MO、背侧TT和腹侧TT，使视蛋白在神经元中表达。这些小鼠被训练用一系列光刺激来按压杠杆，光刺激由8个脉冲(持续时间为3ms)组成，以25赫兹的频率传递，这将阶段性地兴奋神经元。小鼠很快学会了每天超过5次的杠杆式按压(每次30分钟)。特别是，在DPRL、DP和MO接受光刺激的小鼠中观察到强烈的反应。为了确定MN的哪些投射区域在调节奖赏效应中起重要作用，小鼠将AAV-ChR2注射到MN，并在MN的几个投射区域放置光纤。在背侧纹状体内侧部分接受光刺激的小鼠的反应速度很快。我们的研究发现，MN神经元的激活诱导奖赏，MN向内侧背侧纹状体的投射在积极情绪中起着重要作用。

The medial network (MN) of the anterior cortex, including the prelimbic (PrL), intralimbic (IL), and medial orbital (MO) areas, has been implicated in affective disorders such as depression. In addition, the MN may include in rodents the tenia tecta (TT), because the TT, just like other MN structures, is reciprocally connected with the PrL, IL and MO, and may project to the ventral striatum and lateral hypothalamic area. Little is known about the roles of MN glutamatergic and GABAergic neurons in affective processes. We sought to understand them using optogenetic and behavioral procedures in mice. Male C57BL/6J mice received adeno-associated viral vectors encoding channelrhodopsin-2 (AAV-ChR2) into the PrL, IL, MO, dorsal TT and ventral TT, resulting in expression of the opsin in neurons. These mice were trained to press on a lever with a train of photostimulation consisting of 8 pulses (3 ms duration) delivered at the 25-Hz frequency, which phasically excited neurons. Mice quickly learned to leverpress over 5 daily sessions (30 min per session). In particular, vigorous responses were observed from the mice received photostimulation at the dPrL, DP, and MO. To determine which projection regions of the MN play an important role in mediating rewarding effects, mice received AAV-ChR2 into the MN and optic fibers were placed in several its projection regions. Mice received photostimulation at the medial part of the dorsal striatum responded at a high rates. Our research found that the activation of MN neurons induces reward and that the projection from the MN to the medial dorsal striatum plays an important role in positive affect.