The lab is interested in understanding molecular and cellular mechanisms underlying synapse formation and synaptic plasticity, and in the long term elucidating synaptic mechanisms underlying neuronal circuit function in animal behavior. We believe that these studies will provide fundamental insights into neural underpinnings for learning and memory, and will identify synaptic and neural circuit malfunctions that are involved in many neurological and mental disorders, such as Alzheimer's disease, depression and autism. Specifically, during the 2016 fiscal year, we have made following progress: For research Aim 1: we have successfully determined the role of GSG1L, a tetraspanning protein that binds to AMPARs, in the regulation of excitatory synaptic strength and animal behavior. Currently a manuscript for this work has been published in Nature Communications and another manuscript is under revision. In addition, we have made substantial progress in determining the role of FRRS1L, a novel and unexplored membrane protein in the regulation of AMPA receptor trafficking and function. For research Aim 2, we have identified two novel proteins interacting with NMDA receptors. Currently we have made substantial progress in determining the function of one of the two protein-protein interactions in the regulation of excitatory synaptic transmission and synaptic plasticity. For research Aim 3: we have revealed several key molecular processes that are critical for the development of inhibitory synapses. We found that activities of glutamate receptors in developing neurons are crucial for inhibitory synapse development. Current a manuscript for this work has been published in Cell reports. In addition, we have determined the role of cell adhesion molecules in the regulation of inhibitory synapse development. Currently, a manuscript for this work is under preparation. For research Aim 4, we have completed series of behavioral experiments in the mutant mice in which the majority of glutamatergic input onto midbrain dopamine neurons has been genetically inactivated. These experiments demonstrate that glutamatergic input onto dopamine neurons plays a specific and prominent role in behavioral processes that require high-level motivation. Currently, a manuscript about this work has been submitted for peer review. Finally, during the 2016 fiscal year, we have collaborated with Dr. Katherine Roche group at NINDS, NIH to study the function of diseased-associated mutations in NMDA receptors. In addition, we collaborated with Dr. Veronica Alvarez lab at NIAAA, NIH and Dr. Thomas Hnasko lab at UCSD to study the mutant mice lacking glutamatergic input onto dopamine neurons.