A midbrain-reticulotegmental circuit underlies exaggerated startle under fear emotions

本文揭示了从中缝背核(DRN)到惊吓控制中心网状被盖核(RtTg)的神经投射，该投射介导了恐惧条件下的增强惊吓反应。在RtTg中，我们识别了一个抑制微通路，包括RtTgP(RtTgP)的GABA能神经元和RtTgC(RtTgC)的谷氨酸能神经元。抑制RtTgP-RtTgC微通路导致惊吓振幅升高。此外，我们证明了条件性恐惧激活的DRN 5-HT能神经元向RtTgP GABA能神经元发送抑制性投射，这反过来上调RtTgC谷氨酸能神经元的神经元活动。DRN-RtTgP投射的化学遗传激活模拟了恐惧情绪下增加的惊吓反应。此外，从RtTgP GABA能神经元条件性删除5-HT1B受体在很大程度上逆转了条件性恐惧时的惊吓夸张。This study uncovers the neural projection from the dorsal raphe nucleus (DRN) to the reticular tegmental nucleus (RtTg), the startle control center, which mediates the enhanced startle response during fear conditioning. Within the RtTg, we identified an inhibitory microcircuit comprising GABAergic neurons in the RtTgP and glutamatergic neurons in the RtTgC. Inhibition of the RtTgP-RtTgC microcircuit leads to increased startle amplitude. Furthermore, we demonstrated that DRN 5-HTergic neurons activated by fear conditioning send inhibitory projections to GABAergic neurons in the RtTgP, which subsequently upregulates the neuronal activity of glutamatergic neurons in the RtTgC. Chemogenetic activation of the DRN-RtTgP projection mimics the enhanced startle response observed under fear conditioning. Additionally, conditional deletion of the 5-HT1B receptor from GABAergic neurons in the RtTgP largely reverses the exaggerated startle response during fear conditioning.