Optogenetic investigations of motivational circuits in rats and mice

点击翻译按钮获取中文摘要

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.