Despite recent advances in our understanding of the formation and plasticity of cortical circuits mediated by excitatory (glutamate) and inhibitory (GABA) neurotransmitters, how neuromodulators such as dopamine and serotonin regulate neuronal wiring in a developing circuit and ultimately influence an animal’s behavior remain largely unknown. Our goal is to understand at the synaptic and circuit level how neuromodulators fine-tune initial establishment of neuronal circuitry during development and whether early dysregulation of neuromodulatory signaling gives rise to the pathogeneses of neurological disorders such as autism, schizophrenia, and depression. We address these questions with cell-type and synapse-specific resolution by utilizing cutting-edge multidisciplinary techniques that include: in vivo and slice two-photon imaging, two-photon two-color uncaging, slice electrophysiology, optogenetics, chemogenetics, and mouse behavior.