Optogenetic investigations of motivational circuits in rats and mice

大鼠和小鼠激励回路的光遗传学研究

• 批准号: 8933856
• 负责人: SATOSHI IKEMOTO
• 金额: $ 61.14万
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8933856
• 关键词: Affect; Affective; Anterior; Area; Behavioral; Cell Nucleus; Corpus striatum structure; Dopamine; Dorsal; Fiber Optics; Frequencies; Genus Tenia; Glutamates; Investigation; Lateral Hypothalamic Area; Learning; Medial; Mediating; Mental Depression; Mood Disorders; Mus; Neurons; Opsin; Physiologic pulse; Play; Procedures; Process; Rattus; Research; Research Personnel; Rewards; Rodent; Role; Structure; Tectum Mesencephali; Training; Ventral Striatum; adeno-associated viral vector; cell type; gamma-Aminobutyric Acid; male; motivational processes; neural circuit; optogenetics; raphe nuclei; response

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.

前皮层的内侧网络（MN），包括边缘前区（PrL）、边缘内区（IL）和内侧眶区（MO），与抑郁症等情感性障碍有关。此外，在啮齿类动物中，颞叶皮层可能包括颞叶皮层（TT），因为TT与其他颞叶皮层结构一样，与PrL、IL和MO相互连接，并可能投射到腹侧纹状体和外侧下丘脑区。我们对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。我们试图利用小鼠的光遗传学和行为程序来了解它们。