Deciphering and manipulating the cellular signaling circuits for feeding behaviors using approaches including electrophysiology, pharmacogenetics and optogenetics.
At the newly established Molecular Cellular Neuropsychiatry Laboratory at Upstate, directed by Dr. Yao, the mission is to find out how psychiatric diseases damage brain cells and their proper wiring, and how these impairments cause mental illnesses. Our hypothesis is that impaired assembly, function, and plasticity of synapses (small junctions that permit nerve cells to pass an electrical or chemical signal from one to another) and neural circuits underlie cognitive, memory, and emotional deficits of essentially all neuropsychiatric diseases. We are investigating this hypothesis using a number of state-of-the-art molecular, cellular, and electrophysiological technologies on genetically engineered mouse models and induced pluripotent stem cells (iPS cells) derived from human patients. Our major interests are addiction, schizophrenia, autism, and primarily prefrontal cortex related brain and mental diseases. Our previous work done at Harvard Medical School has identified new brain signaling pathways that regulate synapse formation and stabilization and neural circuit rewiring that provide fundamental breakthroughs about the pathogenesis of these diseases. At SUNY Upstate we will continue our cutting-edge research, and the knowledge obtained will be an prerequisite for development of more effective treatment strategies for these diseases.
Jakovcevski M, Ruan H, Shen EY, Dincer A, Javidfar B, Ma Q, Peter CJ, Cheung I, Mitchell AC, Jiang Y, Pothula V, Stewart F, Ernst P, Yao WD*, Akbarian S*. (2015) Neuronal kmt2a/mll1 histone methyltransferase is essential for prefrontal synaptic plasticity and working memory. J Neurosci, 35:5097-108. (*Co-corresponding authors).
Gascon E, Lynch K, Ruan H, Verheyden J, Sun D, Jiao J, Jakovcevksi M, Tapper, AR, Akbarian S, Yao WD, Gao FB. (2014) Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia. Nat Med 20:1444-51.
Zhang JP*, Saur TX*, Duke AN, Grant SG, Platt DM, Rowlett JK, Isacson O, Yao WD. (2014) Motor impairments, striatal degeneration, and altered dopamine-glutamate interplay in mice lacking PSD-95. J Neurogenet, 28:98-111.
Ruan H, Saur TX, Yao WD. (2014) Dopamine-enabled anti-Hebbian timing-dependent plasticity in prefrontal circuitry. Front Neural Circuits. Apr 23;8:38. doi: 10.3389/fncir.2014.00038.
Shulha HP, Crisci J, Reshetov D, Cheung I, Bharadwaj R, Chou HJ, Peter CJ, Houston I, Yao WD, Myers RH, Chen JF, Preuss TM, Rogaev E, Jensen JD, Weng Z, Akbarian S. (2012) Human-specific histone methylation signatures at transcription start sites in prefrontal neurons. PLoS Biol; 10(11):e1001427.
Xu TX, Yao WD. (2010) D1 and D2 dopamine receptors in separate circuits cooperate to drive associative long-term potentiation in the prefrontal cortex. Proc Natl Acad Sci U S A; 107:16366-71.
Xu TX, Sotnikova TD, Liang C, Zhang J, Jung JU, Spealman RD, Gainetdinov RR, Yao WD. (2009) Hyperdopaminergic tone erodes prefrontal LTP via a D2 receptor-operated protein phosphatase gate. J Neurosci; 29:14086-99.
Zhang JP, Vinuela A, Neely MH, Grant SG, Miller GM, Isacson O, Caron MG, Yao WD. (2007) Inhibition of the dopamine D1 receptor signaling by PSD-95. J Biol Chem; 282:15778-89.
Research demonstrates a highly predictive relationship between alcohol exposure of an unborn child during pregnancy and the chance of later alcohol abuse during the already “at risk” age of adolescence. Also, the younger these children first experience alcohol the greater the likelihood of continued abuse. Yet, the processes underlying this increasing pattern of alcohol use and abuse are poorly understood. The senses of smell, taste, and oral irritation, which combine to give us our perception of flavor, can be modified by experience throughout life, including during development in the womb. Why is this important? Because we learn through experience by way of flavor cues in amniotic fluid and even a mother’s breast-milk what foods the mother ate and prefers and, in turn, what is presumably good to eat. Unfortunately, this normally beneficial process is also at play when a mother drinks alcohol, and the flavor qualities of the drug are known to be important determinants of preference and intake behavior. Work in our lab focuses on understanding the processes by which exposure of the unborn child during pregnancy induces changes in the systems involved in the preference for alcohol odor and the acceptability of alcohol’s flavor. This, in turn, contributes to the risk of initial alcohol use and continued adolescent abuse. Further, we wish to understand how adolescent experience with the drug increases the fetal effect and causes the alcohol-induced changes to continue into adulthood.