Optogenetic investigations of motivational circuits in rats and mice

点击翻译按钮获取中文摘要

Previous studies show that activation and suppression of dopamine systems elicit reward and aversion respectively. These effects are usually attributed to dopamine neurons in the ventral tegmental area (VTA) and the mesolimbic dopamine system. On the other hand, dopamine neurons in the substantia nigra pars compacta (SNc) and the nigrostriatal system often linked with motor and cognitive control, including the learning of stimulus-response associations. Here we show that excitation and inhibition of dopamine neurons in the SNc elicit reward and aversion. TH-Cre transgenic mice received adeno-associated viral vectors encoding channelrhodopsin2 (ChR2), halorhodopsin (NpHR), or no opsin into the VTA or SNc. Mice with ChR2 quickly learned to respond on the lever that delivered light into the VTA or SNc. And, when the assignment of active and inactive levers was changed, they shifted their lever preference. They also showed place preference to the compartment in which they concurrently received intracranial light. In addition, mice with NpHR avoided the compartment in which they concurrently received intracranial light into the VTA or SNc, while control mice did not. Our findings confirm that the excitation and inhibition of SNc dopamine neurons induces reward and aversion similar to the VTA dopamine neurons. The present data challenge the dichotomous notion that affective processes are mediated by dopamine neurons in the VTA, but not SNc and suggest the role of nigrostriatal projections in motivation and affect. Therefore, SNc dopamine neurons may play motivational and affective aspects of drug addiction such as craving and those of Parkinsons patients (i.e., depression, anhedonia, and apathy).