Optogenetic investigations of motivational circuits in rats and mice

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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.