Mood disorders such as depression or anxiety disorders are the most prevalent psychiatric diseases and represent the highest level of avoidable health-care cost in first world countries. Nonetheless, the biological foundation of these diseases is only poorly understood despite decades of research. Most clinically used antidepressants target the monoamine system and aim at either raising the levels of monoamines (serotonin, norepinephrine, dopamine) in the synaptic cleft through inhibition of reuptake or act on monoaminergic receptors. However, it takes several weeks until an antidepressant effect emerges and there is a high rate of non-responders. In contrast to monoaminergic antidepressants, inhibition of NMDA glutamate receptors with ketamine induces a rapid antidepressant effect and is particularly efficacious in patients with pharmaco-resistant depression. Together, this suggests that monoaminergic antidepressants only indirectly improve mood whereas the glutamate system is directly contributing to mood elevation. Interestingly, inhibition of muscarinic receptors by scopolamine has also been shown to induce a rapid antidepressant effect implicating the cholinergic system as another important neural circuit in mood disorders. We recently discovered several mesopontine cholinergic brain regions that may co-transmit both, acetylcholine and glutamate and project to the amygdala, a brain area crucial in the regulation of emotional behaviors.Here, we aim at dissecting the role of these areas and acetylcholine/glutamate co-transmission in mood disorders using animal models, genetics, viral vectors, CRISPR/Cas9 and behavioral pharmacology.We hypothesize that deletion of either glutamate or ACh release from PBG neurons will result in decreased expression of fear responses.