Activation/silencing of specific brain pathways with modern techniques such as opto/chemo-genetics have transformed our understanding of the neural circuits underlying animal behaviors. In this talk, I will present two studies that underscore the importance of understanding detailed synaptic release patterns in neural circuits besides obtaining activation/silencing results. In the first study, we investigated the synaptic and circuit mechanisms of essential tremor, which is one of the most common neurological disorders. We established a novel genetic essential tremor mouse model by crossing synaptotagmin 2 conditional knockout mice with parvalbumin-Cre mice. Combining mouse genetics, mouse behaviors, viral manipulation, circuit tracing and slice recording techniques, we identified the specific brain region, cell type, brain pathway and synaptic release defects underlying essential tremor. In a parallel independent study, we explored the roles of zona incerta in mice behaviors. We identified that an inhibitory projection from somatostatin neurons in the central amygdala to parvalbumin neurons in the zona incerta is required for fear memory acquisition and remote retrieval.