Wei-Dong Yao, PhD

EDUCATION

RESEARCH ABSTRACT

The Yao Lab studies neural mechanisms underlying reward, affect, and prosocial behaviors in normal and disease conditions, with a focus in dopamine and the prefrontal cortex (PFC). Combining electrophysiology, behavior, optogenetics, and chemogenetics, we investigate how intrinsic and synaptic plasticity and modulation in PFC circuits are impaired in addiction, FTD (frontotemporal dementia), and related brain disorders. Employing molecular and cellular approaches, we also elucidate novel molecular mechanisms that regulate synapse formation, stabilization, and pruning. We use transgenic and viral-transduced mouse models and human iPSC-derived neurons. Current projects include:

(1) Neural circuitry and synaptic mechanisms of lost empathy in FTD.

(2) Molecular pathogenesis and synaptopathy in FTD.

(3) Prefrontal dopaminergic synaptic and circuitry mechanisms in cocaine addiction.

*Postdoc positions available. Contact yaow@upstate.edu to apply*

Selected Publications:

Phillips HL, Dai H, Zajicek AS, Jansen-West L, Petrucelli L, Gao FB, Yao WD. (2023) Dorsomedial prefrontal hypoexcitability underlies lost empathy in frontotemporal dementia. Neuron. 111(6):797-806.e6. doi: 10.1016/j.neuron.2022.12.027. Epub 2023 Jan 12.

Zajicek AS, Ruan H, Dai H, Skolfield MC, Phillips HL, Burnette WJ, Javidfar B, Sun SC, Akbarian S, Yao WD. (2022) Cylindromatosis drives synapse pruning and weakening by promoting macroautophagy through Akt-mTOR signaling. Mol Psychiatry, 27(5):2414-2424. doi: 10.1038/s41380-022-01571-1. Epub 2022 Apr 21.

Ruan H, Yao WD. (2021) Loss of mGluR1-LTD following cocaine exposure accumulates Ca2+-permeable AMPA receptors and facilitates synaptic potentiation in the prefrontal cortex. J Neurogenet 35(4):358-369. doi: 10.1080/01677063.2021.1931180. Epub 2021 Jun 7.

Choi SY, Lopez-Gonzalez R, Krishnan G, Phillips HL, Li AN, Seeley WW, Yao WD, Almeida S, Gao FB. (2019) C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo. Nat Neurosci. 22(6):851-862. doi: 10.1038/s41593-019-0397-0. Epub 2019 May 13.

Ma Q, Ruan H, Peng L, Zhang M, Gack MU, Yao WD. (2017) Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity. Proc Natl Acad Sci U S A; 114(41):E8760-E8769. doi: 10.1073/pnas.1620153114. Epub 2017 Sep 25. F1000Prime Recommended. https://f1000.com/prime/731737130?bd=1

Ruan H, Yao WD. (2017) Cocaine promotes coincidence detection and lowers induction threshold during Hebbian associative synaptic potentiation in prefrontal cortex. J Neurosci 37(4):986-997. doi: 10.1523/JNEUROSCI.2257-16.2016.

Hou Q, Ruan H, Gilbert J, Wang G, Ma Q, Yao WD, Man HY. (2015) MicroRNA miR124 is required for the expression of homeostatic synaptic plasticity. Nat Commun 2015 Dec 1;6:10045. doi: 10.1038/ncomms10045.

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.

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, Xu TX, Hallett PJ, Watanabe M, Grant SGN, Isacson O Yao WD (2009). PSD-95 uncouples dopamine-glutamate interaction in the D1/PSD-95/NMDA receptor complex. J Neurosci 29: 2948-2960.

Beaulieu JM, Sotnikova T, Yao WD, Kockeritz L, Woodgett JR, Gainetdinov RR, Caron MG. (2004). An Akt/Glycogen Synthase Kinase-3 (GSK-3) signaling cascade mediates dopamine action in vivo. Proc Natl Acad Sci U S A 101:5099-5104.

Yao WD, Gainetdinov RR, Arbuckle MI, Sotnikova TD, Beaulieu JM, Cyr M, Torres GE, Grant SGN, Caron MG (2004). Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity. Neuron 41:625-638.

Torres GE#, Yao WD#, Mohn AR, Quan H, Caron MG (2001). Functional interaction between monoamine plasma membrane transporters and the PDZ domain-containing protein PICK1. Neuron 30: 121-134. (#Co-first authors).

Yao WD, Rusch J, Poo MM, Wu CF (2000). Spontaneous acetylcholine secretion from developing growth cones of Drosophila central neurons in culture: effects of cAMP-pathway mutations.  J Neurosci 20: 2626-37.

Links:

UpstateOnline: Empire Innovation Scholar comes to Upstate, by way of Harvard, to unlock mysteries of the brain

Harvard Med School: Protein's Balancing Act May Provide Handle on Psychiatric Disease

The University of Iowa

https://www.upstate.edu/whatsup/2018/0831-putting-heads-together-brain-researchers-collaborate-to-understand-and-battle-dementia-addiction-schizophrenia-and-more.php

https://issuu.com/upstate/docs/magazine-magsummer18rr