Qi Jia, Zhang Shiliang, Wang Hui-Ling, Wang Huikun, de Jesus Aceves Buendia Jose, Hoffman Alexander F, Lupica Carl R, Seal Rebecca P, Morales Marisela
National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, Maryland, USA.
National Institute on Drug Abuse, Electrophysiology Research Section, National Institutes of Health, Baltimore, Maryland, USA.
Nat Commun. 2014 Nov 12;5:5390. doi: 10.1038/ncomms6390.
Electrical stimulation of the dorsal raphe (DR) and ventral tegmental area (VTA) activates the fibres of the same reward pathway but the phenotype of this pathway and the direction of the reward-relevant fibres have not been determined. Here we report rewarding effects following activation of a DR-originating pathway consisting of vesicular glutamate transporter 3 (VGluT3) containing neurons that form asymmetric synapses onto VTA dopamine neurons that project to nucleus accumbens. Optogenetic VTA activation of this projection elicits AMPA-mediated synaptic excitatory currents in VTA mesoaccumbens dopaminergic neurons and causes dopamine release in nucleus accumbens. Activation also reinforces instrumental behaviour and establishes conditioned place preferences. These findings indicate that the DR-VGluT3 pathway to VTA utilizes glutamate as a neurotransmitter and is a substrate linking the DR-one of the most sensitive reward sites in the brain--to VTA dopaminergic neurons.
对中缝背核（DR）和腹侧被盖区（VTA）进行电刺激可激活同一条奖赏通路的纤维，但该通路的表型以及与奖赏相关的纤维方向尚未确定。在此，我们报告了激活一条起源于DR的通路后的奖赏效应，该通路由含有囊泡谷氨酸转运体3（VGluT3）的神经元组成，这些神经元在投射到伏隔核的VTA多巴胺能神经元上形成不对称突触。对该投射进行光遗传学VTA激活可在VTA中脑伏隔核多巴胺能神经元中引发AMPA介导的突触兴奋性电流，并导致伏隔核中的多巴胺释放。激活还会强化工具性动作并建立条件性位置偏好。这些发现表明，从DR到VTA的VGluT3通路利用谷氨酸作为神经递质，并且是将DR（大脑中最敏感的奖赏位点之一）与VTA多巴胺能神经元相连接的一个底物。
