Zhu's lab enjoy developing new experimental approaches that combine cutting-edge techniques, including rapid recombinant DNA delivery and replacement, multiple whole-cell recordings, genetically encoded sensors, single- and two-photon microscopy-based optogenetics and imaging, single-molecule force spectroscopy and immunoelectron microscopy. These technologies allow them to decipher the molecular and cellular regulations (e.g., nanoscale Ras/MAPK signaling) of synapses in neural circuits, as well as the organization and functions (e.g., salience selection) of neural circuits (Wang G, Wyskiel D, et al. (2015) Nature Protocols 10:397-412). Genetic defects of many signaling molecules are linked to a number of cognitive disorders, e.g., Akt/PKB and calcineurin with schizophrenia, BRaf with cardio-facio-cutaneous syndrome, Brag/IQSec with nonsyndromic X-linked mental retardation, CaMKII with Angelman syndrome, H-Ras with Costello syndrome, p38MAPK and JNK with Alzheimer's disease, PI3K with fragile X syndrome, PTEN with autism, Cowden and Bannayan-Riley-Ruvalcaba syndromes, RasGap NF1 with neurofibromatosis, Rsk with Coffin-Lowry syndrome and X-linked mental retardation, SHP-2 with Noonan syndrome, and tuberin with tuberous sclerosis. Altered interneuronal function is a common mechanism contributing to various neurological, mental and psychiatric disorders, including autisms, epilepsy, depression, Huntington’s disease, neurofibromatosis, schizophrenia, Tourette’s syndrome and trauma (Stornetta and Zhu, Neuroscientist 17: 54-78). Therefore, the findings from their research should guide the future development of treatments for these insidious diseases.