Dr. Huang and his colleagues plan to study how the MECP2 gene regulates brain circuitry — information that may have implications for both Rett syndrome and autism. They intend to look for defects in synapse number and connectivity patterns in a mouse model of Rett syndrome by evaluating changes in the structure and function of inhibitory neurons. They plan to determine the properties of these cells using a short-lived green fluorescent protein that monitors the production of a key enzyme needed for the synthesis of GABA, the major inhibitory transmitter in the brain. The researchers plan to also measure the electrical current in the inhibitory neurons and their targets to determine whether MECP2 is necessary for a cell's normal activity and for the operation of neural circuits. MECP2 encodes a protein that regulates gene expression, but few of its target genes are known. Huang and his team also plan to look for candidates by measuring gene expression levels in specific inhibitory neuron types, in normal and MECP2-deficient neurons, with microarrays, using a technique that they pioneered. Based on these experiments, the researchers may find that mutations in MECP2 lead to weak or aberrant signaling between cells that disrupt the brain circuitry, potentially causing the behavioral, social and cognitive defects associated with Rett syndrome and autism.