Yi-Mei (Amy) Yang
,
Credentials
PhD

Associate Professor
Principal Investigator
Biography

Research Summary

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.

Selected Publications

Chao, O. Y., Pathak, S. S., Zhang, H., Augustine, G. J., Christie, J. M., Kikuchi, C., Taniguchi, H., Yang, Y. M. (2023). Social memory deficit caused by dysregulation of the cerebellar vermis. Nature Communications, 14 6007: 1-19. PMID: 37752149. doi: https://doi.org/10.1038/s41467-023-41744-2 

Levings, D. C., Pathak, S. S., Yang Y. M., Slattery M. (2023). Limited expression of Nrf2 in neurons across the central nervous system. Redox Biology, 65 102830: 1-8. PubMed ID: 37544245. doi: https://doi.org/10.1016/j.redox.2023.102830

Rudolph S., Badura A., Lutzu S., Pathak S. S., Thieme A., Verpeut J. L., Wagner M. J., Yang Y. M., Fioravante D. (2023). Cognitive-affective functions of the cerebellum. The Journal of Neuroscience, 43 (45): 7554-7564. PMID: 37940582. doi: https://www.jneurosci.org/content/43/45/7554

Chao, O. Y., Nikolaus, S., Yang, Y. M.*, Huston, J. P. (2022). Neuronal circuitry for recognition memory of object and place in rodent models. Neuroscience & Biobehavioral Reviews, 141 (104855): 1-30. PMID: 36089106. doi: https://doi.org/10.1016/j.neubiorev.2022.104855 (*Co-corresponding author)

Fang, K., Liu, D., Pathak, S. S., Yang, B., Li, J., Karthikeyan, R., Chao, O. Y., Yang, Y. M.*, Jin, V. X., Cao, R. (2021). Disruption of circadian rhythms by ambient light during neurodevelopment leads to autistic-like molecular and behavioral alterations in adult mice. Cells, 10 (12), 3314-3333. PMID: 34943821. doi: https://doi.org/10.3390/cells10123314 (*Co-corresponding author)

Chao, O. Y., Zhang, H., Pathak, S. S., Huston, J. P., Yang, Y. M. (2021). Functional convergence of motor and social processes in lobule IV/V of the mouse cerebellum. Cerebellum, 20: 836–852. PMID: 33661502. doi: https://doi.org/10.1007/s12311-021-01246-7 

Chao, O. Y., Pathak, S. S., Zhang, H., Dunaway, N., Li, J. S., Mattern, C., Nikolaus, S., Huston, J. P., Yang, Y. M. (2020). Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism. Molecular Brain, 13: 1-16. PMID: 32778145. doi: https://doi.org/10.1186/s13041-020-00649-7 

Chao, O. Y., de Souza Silva, M. A., Yang, Y. M.*, Huston, J. P. (2020). 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. Neuroscience and Biobehavioral Reviews, 113: 373-407. PMID: 32298711. doi: https://doi.org/10.1016/j.neubiorev.2020.04.007 (*Co-corresponding author)

Chao, O. Y., de Marron Fernandez Velasco, E., Pathak, S. S., Maitra, S., Zhang, H., Duvick, L., Wickman, K., Orr, H. T., Hirai, H., Yang, Y. M. (2020). Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism. Neuropsychopharmacology, 45 (7): 1159-1170. PMID: 32179875. doi: https://doi.org/10.1038/s41386-020-0656-5 

Lesperance, L. S., Yang, Y. M., Wang, L. Y. (2020). Delayed expression of activity-dependent gating switch in synaptic AMPARs at a central synapse. Molecular Brain, 13: 1-18. PMID: 31941524. doi: https://doi.org/10.1186/s13041-019-0536-2 

Chao, O. Y., Yang, Y. M. (2019). Timing constraints of action potential evoked Ca2+ current and transmitter release at a central nerve terminal. Scientific Reports, 9: 1-14. PMID: 30872753. doi: https://doi.org/10.1038/s41598-019-41120-5 

Fekete, A., Nakamura, Y., Yang, Y. M., Herlitze, S., Mark, M. D., DiGregorio, D. A., Wang, L. Y. (2019). Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules. Nature Communications, 10 (1): 826-842. PMID: 30778063. doi: https://doi.org/10.1038/s41467-019-08452-2 

Chao, O. Y., Yunger, R., Yang, Y. M. (2018). 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. Behavioural Brain Research, 347: 140-147. PMID: 29545145. doi: https://doi.org/10.1016/j.bbr.2018.03.014 

Yang, Y. M.*, Arsenault, J., Bah, A., Krzeminski, M., Fekete, A., Chao, O. Y., Pacey, L. K., Wang, A., Forman-Kay, J., Hampson, D. R., Wang, L. Y. (2020). (Epub 2018) Identification of a molecular locus for normalizing dysregulated GABA release from interneurons in the Fragile X brain. Molecular Psychiatry, 25 (9): 2017-2035. PMID: 30224722. doi: https://doi.org/10.1038/s41380-018-0240-0 (*Co-corresponding author)

Yang, Y. M., Wang, W., Fedchyshyn, M. J., Zhou, Z., Ding, J., Wang, L. Y. (2014). Enhancing the fidelity of neurotransmission by activity-dependent facilitation of presynaptic potassium currents. Nature Communications, 5: 1-13. PMID: 25078759. doi: https://doi.org/10.1038/ncomms5564 .

Yang, Y. M., Aitoubah, J., Lauer, A. M., Nuriya, M., Takamiya, K., Jia, Z., May, B. J., Huganir, R. L., Wang, L. Y. (2011). GluA4 is indispensable for driving fast neurotransmission across a high-fidelity central synapse. The Journal of Physiology, 589 (17): 4209-4227. PMID: 21690196. doi: https://doi.org/10.1113/jphysiol.2011.208066 

Zhang, B., Sun, L., Yang, Y. M., Huang, H. P., Zhu, F. P., Wang, L., Zhang, X. Y., Guo, S., Zuo, P. L., Zhang, C. X., Ding, J. P., Wang, L. Y., Zhou, Z. (2011). Action potential bursts enhance transmitter release at a giant central synapse. The Journal of Physiology, 589 (9): 2213-2227. PMID: 21486773. doi: https://doi.org/10.1113/jphysiol.2010.200154 

Yang, Y. M., Fedchyshyn, M. J., Grande, G., Aitoubah, J., Tsang, C. W., Xie, H., Ackerley, C. A., Trimble, W. S., Wang, L. Y. (2010). Septins regulate developmental switching from microdomain to nanodomain coupling of Ca2+ influx to neurotransmitter release at a central synapse. Neuron, 67 (1): 100-115. PMID: 20624595. doi: https://doi.org/10.1016/j.neuron.2010.06.003 

Wang, L. Y., Fedchyshyn, M. J., Yang, Y. M. (2009). Action potential evoked transmitter release in central synapses: Insights from the developing calyx of Held. Molecular Brain, 2: 1-11. PMID: 19939269. doi: https://doi.org/10.1186/1756-6606-2-36 

Joshi, I., Yang, Y. M.*, Wang, L. Y. (2007). 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. The Journal of Neuroscience, 27 (37): 9989-9999. PMID: 17855613. doi: https://doi.org/10.1523/JNEUROSCI.2506-07.2007 (*Co-first author)

Yang, Y. M., Wang, L. Y. (2006). Amplitude and kinetics of action potential-evoked Ca2+ current and its efficacy in triggering transmitter release at the developing calyx of Held synapse. The Journal of Neuroscience, 26 (21): 5698-5708. PMID: 16723526. doi: https://doi.org/10.1523/JNEUROSCI.4889-05.2006

Education

PhD, Huazhong University of Science and Technology, Tongji Medical School
Major: Pharmacology
BS, Hebei Medical University
Major: Pharmacy

Fellowships, Residencies, and Visiting Engagements

Postdoctoral Fellow, Fellowship
University of Toronto
Canada
Postdoctoral Fellow, Fellowship
Oregon Health & Science University
United States

Honors and Recognition

Assistant Professor Award, University of Minnesota Foundation
2017
Trainee Travel Award, SickKids Research Institute
2011
Brain Star Award, Canadian Institutes of Health Research
2010
Selected Publications

Selected Publications

Rudolph S., Badura A., Lutzu S., Pathak S. S., Thieme A., Verpeut J. L., Wagner M. J., Yang Y. M., Fioravante D., 2023. Cognitive-affective functions of the cerebellum. The Journal of Neuroscience,. 43 (45): 7554-7564.
doi: https://www.jneurosci.org/content/43/45/7554 PubMed ID: 37940582.
Chao, O. Y. , Pathak, S. S., Zhang, H., Augustine, G. J., Christie, J. M, Kikuchi, C., Taniguchi, H., Yang, Y. M. , 2023. Social memory deficit caused by dysregulation of the cerebellar vermis. Nature Communications, 14 (6007): 1-19.
doi: https://doi.org/10.1038/s41467-023-41744-2 PubMed ID: 37752149.
Levings, D. C., Pathak, S. S., Yang Y. M., Slattery M., 2023. Limited expression of Nrf2 in neurons across the central nervous system. Redox Biology, 65 (102830): 1-8.
doi: https://doi.org/10.1016/j.redox.2023.102830 PubMed ID: 37544245.
Chao, O. Y, Nikolaus, S., Yang, Y. M, Huston, J. P., 2022. Neuronal circuitry for recognition memory of object and place in rodent models. Neuroscience & Biobehavioral Reviews, 141 (104855): 1-30.
Fang, K., Liu, D., Pathak, S. S., Yang, B., Li, J., Karthikeyan, R., Chao, O. Y., Yang, Y. M., Jin, V. X., Cao, R., 2021. Cells, 10 (12): 3314.
doi: https://doi.org/10.3390/cells10123314 PubMed ID: 34943821.
Gurma, M., Yang, Y. M., Wang, L. Y., 2021. Developmental plasticity of NMDA receptors at the calyx of Held synapse. Neuropharmacology, 196 1-10.
Li, J. S., Yang, S. S., Huston, J. P., Chao, O. Y., Yang, Y. M., Mattern, C., 2021. Acute intranasal dopamine application counteracts the reversal learning deficit of spontaneously hypertensive rats in an attentional set-shifting task. Psychopharmacology, 238 (9): 2419-2428.
doi: https://doi.org/10.1007/s00213-021-05863-2 PubMed ID: 33982142.
Chao, O. Y., Zhang, H., Pathak, S. S., Huston, J. P., Yang, Y. M., 2021. Functional convergence of motor and social processes in lobule IV/V of the mouse cerebellum.. Cerebellum, 20 836–852.
doi: https://doi.org/10.1007/s12311-021-01246-7 PubMed ID: 33661502.
Yang, Y. M., Arsenault, J., Bah, A., Krzeminski, M., Fekete, A., Chao, O. Y., Pacey, L. K., Wang, A., Forman-Kay, J., Hampson, D. R., Wang, L. Y., 2020. Identification of a molecular locus for normalizing dysregulated GABA release from interneurons in the Fragile X brain.. Molecular Psychiatry, 25 (9): 2017-2035.
doi: https://doi.org/10.1038/s41380-018-0240-0 PubMed ID: 30224722.
Chao, O. Y., Pathak, S. S., Zhang, H., Dunaway, N., Li , J. S., Mattern, C., Nikolaus, S., Huston, J. P., Yang, Y. M., 2020. Altered dopaminergic pathways and therapeutic effects of intranasal dopamine in two distinct mouse models of autism.. Molecular Brain, 13 1-16.
doi: https://doi.org/10.1186/s13041-020-00649-7 PubMed ID: 32778145.
Chao, O. Y., de Souza Silva, M. A., Yang, Y. M., Huston, J. P., 2020. 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.. Neuroscience and biobehavioral reviews, 113 373-407.
Chao, O. Y., de Marron Fernandez Velasco, E., Pathak, S. S., Maitra, S., Zhang, H., Duvick, L., Wickman, K., Orr, H. T., Hirai, H., Yang, Y. M., 2020. Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism.. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 45 (7): 1159-1170.
doi: https://doi.org/10.1038/s41386-020-0656-5 PubMed ID: 32179875.
Lesperance, L. S., Yang, Y. M., Wang, L. Y., 2020. Delayed expression of activity-dependent gating switch in synaptic AMPARs at a central synapse.. Molecular Brain, 13 1-18.
doi: https://doi.org/10.1186/s13041-019-0536-2 PubMed ID: 31941524.
Chao, O. Y., Yang, Y. M., 2019. Timing constraints of action potential evoked Ca2+ current and transmitter release at a central nerve terminal.. Scientific Reports, 9 1-14.
doi: https://doi.org/10.1038/s41598-019-41120-5 PubMed ID: 30872753.
Fekete, A., Nakamura, Y., Yang, Y. M., Herlitze, S., Mark, M. D., DiGregorio, D. A., Wang, L. Y., 2019. Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules.. Nature Communications, 10 (1): 826-842.
doi: https://doi.org/10.1038/s41467-019-08452-2 PubMed ID: 30778063.
Wang, A. L., Chao, O. Y., Yang, Y. M., Trossbach, S. V., MĂĽller, C. P., Korth, C., Huston, J. P., de Souza Silva, M. A., 2019. Anxiogenic-like behavior and deficient attention/working memory in rats expressing the human DISC1 gene.. Pharmacology, Biochemistry, and Behavior, 179 73-79.
doi: https://doi.org/10.1016/j.pbb.2019.02.005 PubMed ID: 30779934.
Chao, O. Y., Yunger, R., Yang, Y. M., 2018. 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.. Behavioural Brain Research, 347 140-147.
doi: https://doi.org/10.1016/j.bbr.2018.03.014 PubMed ID: 29545145.
Yang, Y. M., Wang, L. Y., 2017. Ageing brains attend a symphony with asynchronous transmitter release.. The Journal of Physiology, 595 (3): 613-614.
doi: https://doi.org/10.1113/JP273421 PubMed ID: 28145009.
Yang, Y. M., Wang, W., Fedchyshyn, M. J., Zhou, Z., Ding, J., Wang, L. Y., 2014. Enhancing the fidelity of neurotransmission by activity-dependent facilitation of presynaptic potassium currents.. Nature Communications, 5 1-13.
doi: https://doi.org/10.1038/ncomms5564 PubMed ID: 25078759.
Wang, W., Luo, J., Hou, P., Yang, Y. M., Xiao, F., Yuchi, M., Qu, A., Wang, L. Y., Ding, J., 2013. Native gating behavior of ion channels in neurons with null-deviation modeling.. PloS One, 8 (10): 1-10.
Yang, Y. M., Aitoubah, J., Lauer, A. M., Nuriya, M., Takamiya, K., Jia, Z., May, B. J., Huganir, R. L., Wang, L. Y., 2011. GluA4 is indispensable for driving fast neurotransmission across a high-fidelity central synapse.. The Journal of Physiology, 589 (17): 4209-4227.
Zhang, B., Sun, L., Yang, Y. M., Huang, H. P., Zhu, F. P., Wang, L., Zhang, X. Y., Guo, S., Zuo, P. L., Zhang, C. X., Ding, J. P., Wang, L. Y., Zhou, Z., 2011. Action potential bursts enhance transmitter release at a giant central synapse.. The Journal of Physiology, 589 (9): 2213-2227.
Yang, Y. M., Fedchyshyn, M. J., Grande, G., Aitoubah, J., Tsang, C. W., Xie, H., Ackerley, C. A., Trimble, W. S., Wang, L. Y., 2010. Septins regulate developmental switching from microdomain to nanodomain coupling of Ca(2+) influx to neurotransmitter release at a central synapse.. Neuron, 67 (1): 100-115.
Wang, L. Y., Fedchyshyn, M. J., Yang, Y. M., 2009. Action potential evoked transmitter release in central synapses: Insights from the developing calyx of Held.. Molecular Brain, 2 1-11.
doi: https://doi.org/10.1186/1756-6606-2-36 PubMed ID: 19939269.
Joshi, I., Yang, Y. M., Wang, L. Y., 2007. 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.. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 27 (37): 9989-9999.
Yang, Y. M., Wang, L. Y., 2006. Amplitude and kinetics of action potential-evoked Ca2+ current and its efficacy in triggering transmitter release at the developing calyx of Held synapse.. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 26 (21): 5698-5708.
Chen, S., Yang, Y., Zhang, L., Pang, X., Dai, Z., Zeng, F., 2000. A sensitive HPLC technique for the quantitation of dauricine.. Journal of Tongji Medical University, 20 39-42.
doi: https://doi.org/10.1007/bf02887672 PubMed ID: 12845753.
Chen, S., Liu, L., Yang, Y., Dai, Z., Zeng, F., 2000. Metabolism of dauricine and identification of its main metabolites.. Journal of Tongji Medical University, 20 (3): 253-256.
doi: https://doi.org/10.1007/bf02887006 PubMed ID: 11215064.
Chao, O. Y., Pathak, S. S., Zhang, H., Augustine, G. J., Christie, J. M., Kikuchi, C., Taniguchi, H., Yang, Y. M., Social memory deficit gated by dysregulation of the cerebellar vermis. Nature Communications,
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1035 University Drive
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