Emotional behaviors are regulated by many brain processes such as synaptic transmission and neuroimmune communication. Dysregulation of these processes leads to brain disorders including depression. Advances in this area have identified key brain substrates and circuits that control emotional behaviors, paving the path to mental wellness of these patients. More recently, mounting evidence has shown that mood can be modulated by neurohormonal and neuroimmune status, as such, perturbation of hormonal and immune systems can markedly impact on mood and increase the incidence of depression. In this symposium titled “Neuromodulation of mood and its alteration in brain disorders”, we invite investigators working on this topic to lead a discussion on unconventional aspects of this neuromodulation, aiming to stimulate ideas that could translate these findings to a better treatment of brain disorders including depression. The symposium will be co-chaired by Prof. Kleinridders (University of Potsdam, Germany) and postdoc trainee Dr. Chen (Harvard Medical School, USA). The other two invited speakers include Dr. Zhang (Tsinghua University, China) and Dr. Fulton (Universite de Montreal, Canada). Prof. Kleinridders started his lab in Germany in May 2015 and is now a full professor, focusing on understanding how brain insulin resistance impacts on mood and whether applying nutritional interventions can reverse depression. His recent work mainly published on Antioxidants, Molecular Metabolism, JCI Insights, Lancet Diabetes Endocrinol, etc. In this symposium, he will be talking about the crosstalk of nutrition and insulin action on brain metabolism and mood modulation. Dr. Chen started his second postdoc in October 2019 with Dr. C Ronald Kahn at Harvard Medical School. He mainly works on revealing cellular heterogeneity of brain reward system and molecular factors underly comorbidity of diabetes and brain disorders. His previous work mainly published on Nature communications, Nature Neuroscience, Science Advances, PNAS, and Trends in Neuroscience. He will be talking about the crosstalk of microglia and astrocytes regulated by insulin and how its dysregulation leads to mood and cognitive disorders. Dr. Zhang will finish her postdoc training with Prof. Guoping Feng at MIT soon and start her own lab in January 2023, as an assistant professor at Tsinghua University. She mainly works on identifying thalamic substrates that modulate motor, mood, and cognition. As a rising star in the area of neurological diseases, her recent work was published on Nature and highlighted by major media sources. Her other work was published on Neuron, Nature Communications, Nature Medicine, and Nature Reviews Neuroscience. In this symposium, she will be talking about her unpublished work on Cholinergic modulation of mood and behavior in neurological disease models. These talks will expand our current understanding of neuromodulation of mood/behavior to deeper levels that involve various neuromodulations (insulin, serotonergic, and cholinergic systems). Further, these talks will connect these mechanisms to neural and immune interaction. In summary, we anticipate the IBNS participants will learn from this symposium and stimulate collaborations for their further research.