Yi-Mei (Amy) Yang
,
Credentials
PhD
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
Fellowships, Residencies, and Visiting Engagements
Honors and Recognition
Selected Publications
Contact
Address
Department of Biomedical SciencesSMED 337
1035 University Drive
Duluth, MN 55812