Abstract：
Stress alters the level of reward evaluation and seeking. However, the neural circuitry mechanisms underlying stress induced effects on natural reward seeking remain unclear. Here we report a septal-accumbens pathway that mediates the effects of acute stress on reward seeking suppression. We first established the sucrose oral self-administration paradigm and measured the effects of acute stress on reward seeking behavior after 21 days of abstinence. Both forced swimming stress and foot shock stress significantly suppressed the natural reward seeking. Among a variety of brain regions, intermediolateral septum (LSi) appear as a strong stress-responsive area containing abundant c-Fos positive cells; chemogenetic inactivation of LSi reinstated the reward seeking behavior. To elucidate the downstream targets receiving LSi projections, we combined pathway-specific retro-labeling and chemogenetic manipulation to confirm the involvement of LSi-nucleus accumbens (NAc) rather than the Ventral tegmental area (VTA) in mediating the observed behavioral responses. In conclusion, the septal-accumbal projection constitute a discrete circuit dictating the stress evoked alterations on reward seeking and may implicate in treatment of stress induced anhedonia.
摘要：
压力会改变奖励评估和寻求的水平。然而,应激诱导的自然奖赏寻求效应的神经回路机制尚不清楚.在这里，我们报告了中隔-伏隔通路，该通路介导了急性压力对寻求奖励抑制的影响。我们首先建立了蔗糖口服自我给药范式，并测量了禁欲21天后急性压力对奖励寻求行为的影响。强迫游泳压力和脚部冲击压力都显着抑制了自然的奖励寻求。在各种大脑区域中，中外侧隔（LSi）表现为强烈的应激反应区，其中含有丰富的c-Fos阳性细胞；LSi的化学遗传学失活恢复了寻求奖励的行为。为了阐明接收LSi投影的下游目标，我们结合了途径特异性的逆向标记和化学遗传学操作，以确认LSi伏隔核（NAc）而不是腹侧被盖区（VTA）参与介导观察到的行为反应。总之,间隔-伏隔投影构成了一个离散的回路，指示了寻求奖励时压力诱发的改变，并可能涉及压力诱发的快感缺失的治疗。
