Yi-Mei (Amy) Yang, PhD

Faculty, Graduate Program in Neuroscience

Faculty, Integrated Biosciences Graduate Program 

Faculty, Developmental Biology Center

Member, Society for Neuroscience 

Synapses are the fundamental units of neural communication in the brain. Using multidisciplinary approaches, we study how synaptic structure and function are precisely shaped during development and how their dysfunctions lead to neurological disorders. By understanding the physio-pathological roles of critical synaptic proteins and ion channels at the cellular, circuitry and system levels, we aim to identify novel targets and further develop pharmacological and genetic therapies for neurodevelopmental disorders, such as autism spectrum disorder (ASD).

ASD is characterized by defective social interactions, impaired communication and restricted patterns of repetitive behaviors. Although ASD involves many brain areas, emerging evidence suggests that aberrant activity of the cerebellum in the early developmental stage can lead to ASD. Employing various autistic mouse models to simulate the complex etiology of ASD, we investigate the cellular and molecular mechanisms underlying the cerebellum pathology. By selectively manipulating the excitability of cerebellar neurons, we ask how dysfunction of the cerebellum affects the brain circuitry and generates the autistic phenotypes over development.

https://www.ncbi.nlm.nih.gov/myncbi/18Q9hDKf42V13M/bibliography/public/

• Yang YM, Arsenault J, Bah A, Krzeminski M, Fekete A, Chao OY, Pacey LK, Wang A, Forman-Kay J, Hampson DR, Wang LY. Identification of a molecular locus for normalizing dysregulated GABA release from interneurons in the Fragile X brain. Mol Psychiatry. 2020 Sep;25(9):2017-2035. doi: 10.1038/s41380-018-0240-0. Epub 2018 Sep 17. PubMed PMID: 30224722; PubMed Central PMCID: PMC7473840.
• Chao OY, Pathak SS, Zhang H, Dunaway N, Li JS, Mattern C, Nikolaus S, Huston JP, Yang YM. Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism. Mol Brain. 2020 Aug 10;13(1):111. doi: 10.1186/s13041-020-00649-7. PubMed PMID: 32778145; PubMed Central PMCID: PMC7418402.
• Chao OY, Marron Fernandez de Velasco E, Pathak SS, Maitra S, Zhang H, Duvick L, Wickman K, Orr HT, Hirai H, Yang YM. Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism. Neuropsychopharmacology. 2020 Jun;45(7):1159-1170. doi: 10.1038/s41386-020-0656-5. Epub 2020 Mar 16. PubMed PMID: 32179875; PubMed Central PMCID: PMC7234983.
• Chao OY, de Souza Silva MA, Yang YM, Huston JP. The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties. Neurosci Biobehav Rev. 2020 Jun;113:373-407. doi: 10.1016/j.neubiorev.2020.04.007. Epub 2020 Apr 13. Review. PubMed PMID: 32298711; PubMed Central PMCID: PMC7302494.
• Lesperance LS, Yang YM, Wang LY. Delayed expression of activity-dependent gating switch in synaptic AMPARs at a central synapse. Mol Brain. 2020 Jan 15;13(1):6. doi: 10.1186/s13041-019-0536-2. PubMed PMID: 31941524; PubMed Central PMCID: PMC6961283.
• Wang AL, Chao OY, Yang YM, Trossbach SV, Müller CP, Korth C, Huston JP, de Souza Silva MA. Anxiogenic-like behavior and deficient attention/working memory in rats expressing the human DISC1 gene. Pharmacol Biochem Behav. 2019 Apr;179:73-79. doi: 10.1016/j.pbb.2019.02.005. Epub 2019 Feb 16. PubMed PMID: 30779934.
• Chao OY, Yang YM. Timing constraints of action potential evoked Ca²⁺ current and transmitter release at a central nerve terminal. Sci Rep. 2019 Mar 14;9(1):4448. doi: 10.1038/s41598-019-41120-5. PubMed PMID: 30872753; PubMed Central PMCID: PMC6418091.
• Fekete A, Nakamura Y, Yang YM, Herlitze S, Mark MD, DiGregorio DA, Wang LY. Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules. Nat Commun. 2019 Feb 18;10(1):826. doi: 10.1038/s41467-019-08452-2. PubMed PMID: 30778063; PubMed Central PMCID: PMC6379440.
• Chao OY, Yunger R, Yang YM. Behavioral assessments of BTBR T+Itpr3tf/J mice by tests of object attention and elevated open platform: Implications for an animal model of psychiatric comorbidity in autism. Behav Brain Res. 2018 Jul 16;347:140-147. doi: 10.1016/j.bbr.2018.03.014. Epub 2018 Mar 13. PubMed PMID: 29545145.
• Yang YM, Wang LY. Ageing brains attend a symphony with asynchronous transmitter release. J Physiol. 2017 Feb 1;595(3):613-614. doi: 10.1113/JP273421. PubMed PMID: 28145009; PubMed Central PMCID: PMC5285715.
• Yang YM, Wang W, Fedchyshyn MJ, Zhou Z, Ding J, Wang LY. Enhancing the fidelity of neurotransmission by activity-dependent facilitation of presynaptic potassium currents. Nat Commun. 2014 Jul 31;5:4564. doi: 10.1038/ncomms5564. PubMed PMID: 25078759; PubMed Central PMCID: PMC4503407.
• Wang W, Luo J, Hou P, Yang Y, Xiao F, Yuchi M, Qu A, Wang L, Ding J. Native gating behavior of ion channels in neurons with null-deviation modeling. PLoS One. 2013;8(10):e77105. doi: 10.1371/journal.pone.0077105. eCollection 2013. PubMed PMID: 24204745; PubMed Central PMCID: PMC3808363.
• Yang YM, Aitoubah J, Lauer AM, Nuriya M, Takamiya K, Jia Z, May BJ, Huganir RL, Wang LY. GluA4 is indispensable for driving fast neurotransmission across a high-fidelity central synapse. J Physiol. 2011 Sep 1;589(17):4209-27. doi: 10.1113/jphysiol.2011.208066. Epub 2011 Jun 20. PubMed PMID: 21690196; PubMed Central PMCID: PMC3180579.
• Zhang B, Sun L, Yang YM, Huang HP, Zhu FP, Wang L, Zhang XY, Guo S, Zuo PL, Zhang CX, Ding JP, Wang LY, Zhou Z. Action potential bursts enhance transmitter release at a giant central synapse. J Physiol. 2011 May 1;589(Pt 9):2213-27. doi: 10.1113/jphysiol.2010.200154. Epub 2011 Feb 28. PubMed PMID: 21486773; PubMed Central PMCID: PMC3098699.
• Yang YM, Fedchyshyn MJ, Grande G, Aitoubah J, Tsang CW, Xie H, Ackerley CA, Trimble WS, Wang LY. Septins regulate developmental switching from microdomain to nanodomain coupling of Ca(2+) influx to neurotransmitter release at a central synapse. Neuron. 2010 Jul 15;67(1):100-15. doi: 10.1016/j.neuron.2010.06.003. PubMed PMID: 20624595; PubMed Central PMCID: PMC5145303.
• Wang LY, Fedchyshyn MJ, Yang YM. Action potential evoked transmitter release in central synapses: insights from the developing calyx of Held. Mol Brain. 2009 Nov 25;2:36. doi: 10.1186/1756-6606-2-36. Review. PubMed PMID: 19939269; PubMed Central PMCID: PMC2794261.
• Joshi I, Yang YM, Wang LY. Coincident activation of metabotropic glutamate receptors and NMDA receptors (NMDARs) downregulates perisynaptic/extrasynaptic NMDARs and enhances high-fidelity neurotransmission at the developing calyx of Held synapse. J Neurosci. 2007 Sep 12;27(37):9989-99. doi: 10.1523/JNEUROSCI.2506-07.2007. PubMed PMID: 17855613; PubMed Central PMCID: PMC6672635.
• Yang YM, Wang LY. Amplitude and kinetics of action potential-evoked Ca2+ current and its efficacy in triggering transmitter release at the developing calyx of Held synapse. J Neurosci. 2006 May 24;26(21):5698-708. doi: 10.1523/JNEUROSCI.4889-05.2006. PubMed PMID: 16723526; PubMed Central PMCID: PMC6675268.