Email: nuo.li@duke.edu
Phone: 919-681-7503
Li Lab
Our goal is to understand how the brain generates volitional movement. A planning phase precedes all volitional movements in which the brain programs appropriate movement on the fly to achieve the goal at hand. This fundamental process dictates our behavior, ranging from speech to motor skills. We study how different brain regions and cell types organize into functional circuits to orchestrate neural dynamics driving volitional movement.
Our work has isolated neural antecedents of volitional movements in the mouse brain (also known as ‘preparatory activity’ or ‘readiness potentials’ in humans). Our ongoing studies outline a distributed network of over a dozen brain areas that mediate planning and execution of volitional movement. To understand neural networks distributed across such a wide scale, we are developing new approaches to map, manipulate, and analyze multi-regional circuits in the intact brain during behavior.
Selected Publications
Gao Z, Davis C, Thomas AM, Economo MN, Abrego AM, Svoboda K, De Zeeuw C, Li N (2018). A cortico-cerebellar loop for motor planning. Nature 563(7729):113-116. https://doi.org/10.1038/s41586-018-0633-x
Chen G, Kang B, Lindsey J, Druckmann S, Li N (2021). Modularity and robustness of frontal cortex networks. Cell, 184(14):3717-3730. https://doi.org/10.1016/j.cell.2021.05.026
Yang W, Tipparaju SL, Chen G, Li N (2022). Orderly and thalamus-driven frontal cortex activity supports decision-making. Nat. Neurosci., 25, 1339-1352. https://doi.org/10.1038/s41593-022-01171-w
Zhu J, Hasanbegović H, Liu LD, Gao Z, Li N (2023) Activity map of a cortico-cerebellar loop underlying motor planning. Nat. Neurosci. 26, 1916-1928. https://doi.org/10.1038/s41593-023-01453-x
Thomas A, Yang W, Wang C, Tipparaju SL, Chen G, Sullivan B, Swiekatowski K, Tatam M, Gerfen C, Li N (2023). Superior colliculus bidirectionally modulates choice activity in frontal cortex. Nat Commun. 14(1):7358. https://doi.org/10.1038/s41467-023-43252-9
Li Lab Members
Alumni
Graduate students
Elise Mangin 2019-2023
Current position: Consultant, Intelispark.
Postdoctoral Fellows
Weiguo Yang, PhD 2016 – 2023
Current position: Assistant Professor, Shanghai Jiao Tong University.
Alyse Thomas, PhD 2017 - 2023 (NIH K01 Awardee, 2020)
Current position: Senior Research Investigator, UPenn Gene Therapy Program
Liu (“Dave”) Liu, PhD 2017 - 2023 (CIHR Fellowship, 2017)
Current position: Data Scientist, OpenSea
Guang Chen, PhD 2017 - 2022
Current position: Assistant Professor, Chinese Institute for Brain Research (CIBR)
Yaoyao Hao, PhD 2017 - 2021
Current position: Research Associate, Zhejiang University
Han Hou, PhD 2020 - 2022
Current position: Scientist, Allen Institute for Neural Dynamics
High-School Students, Undergraduate Students, Master Students, and RAs
Amada M. Abrego 2017 – 2019 Master
Current position: Engineer, UT Health
Courtney Davis 2017-2019 Research Assistant
Current position: research associate at UT Health
Kylie Swiekatowski 2018-2020 Undergraduate
Current position: medical student at UT Health
Mahima Tatam 2018-2020 Undergraduate
Current position: master student at UNT Health Science Center
Kaiwen Wu 2017 Undergraduate
Current position: software engineer at Meta
Li Research
We study neural circuit mechanisms of volitional movement. The way we move has deep social psychological consequences that affect our well-being. A circuit-based understanding of volitional movements will provide a roadmap for treating movement disorders. More broadly, we use volitional movement as a model to understand how multi-regional circuits perform fundamental computations that support cognition. We currently have the following research projects.
Organization of Frontal Cortical Circuits
We have a longstanding interest in analysis of frontal cortical circuits. We recently discovered a redundant modular organization of frontal cortical networks that underly robust short-term memory. Modularity and redundancy are common to robust engineered networks such as modern power grids. These networks continue to perform when parts of the network fail because other redundant parts take over the process. We are currently examining how modular organization maps onto cortical circuits and how such organization creates resilience. In parallel, we are combining two-photon imaging with molecular and connectivity analysis to understand the logics of frontal cortical computation.
Chen G, Kang B, Druckmann S, Li N (2021). Modularity and robustness of frontal cortex networks. Cell 184(14):3717-3730. https://doi.org/10.1016/j.cell.2021.05.026
Our recent work suggests that the cerebellum, classically associated with fine motor control, contributes to preparatory activity in frontal cortex. We also identified hotspots in the cerebellum that reciprocally interact with the frontal cortex to mediate motor planning. We are currently testing the hypothesis that cerebellum shapes frontal cortical activity analogously to how it performs predictive motor control. Specific neocortical activity states encode current states of the world and specific actions within it. The cerebellum learns to use the current pattern of neocortical activity to predict and define a set of possible future activity states in frontal cortex.
Zhu J, Hasanbegović H, Liu DL, Gao Z, Li N (2023). Activity map of a cortico-cerebellar loop underlying motor planning. Nat Neurosci. 26, 1916-1928. https://doi.org/10.1038/s41593-023-01453-x
Gao Z, Davis C, Thomas AM, Economo MN, Abrego AM, Svoboda K, De Zeeuw C, Li N (2018). A cortico-cerebellar loop for motor planning. Nature 563(7729):113-116. https://doi.org/10.1038/s41586-018-0633-x
Appropriate actions are selected through competition between potential choice options. Our recent work has identified a frontal cortico-basal ganglia-superior colliculus network for selection of directional licking during decision-making. Distinct neuronal populations in this multi-regional network encode opposing choice options for lick direction and exhibit push-pull dynamics prior to a licking movement, reflecting choice competition. Our goal is to resolve the circuit logics of this choice competition. We are currently examining how choice activity maps onto cell types in each region, how these circuits interact in a topographically confined fashion, and how their activities impinge upon the broader network dynamics.
Thomas A, Yang W, Wang C, Tipparaju SL, Chen G, Sullivan B, Swiekatowski K, Tatam M, Gerfen C, Li N (2023). Superior colliculus bidirectionally modulates choice activity in frontal cortex. Nat Commun. 14(1):7358. https://doi.org/10.1038/s41467-023-43252-9
Yang W, Tipparaju SL, Chen G, Li N (2022). Thalamus-driven functional populations in frontal cortex support decision-making. Nat Neurosci. 25, 1339-1352. https://doi.org/10.1038/s41593-022-01171-w
Orofacial movements, such as breathing, chewing, and swallowing, are controlled by distinct oscillator circuits in the brainstem. These oscillators are tightly coordinated with each other. Disorganization of their rhythms leads to severe consequences such as choking, which is a leading cause of death among clinical populations and elderly. Our understanding of brainstem circuits is limited by existing neurophysiological recordings. Moreover, current neurophysiology is not yet integrated with emerging tools in connectivity and transcriptomic analyses. We are developing methods for brainstem Neuropixels recordings in behaving mice and combining them with molecular analysis to dissect the neural oscillators for orofacial rhythms.
Liu LD, Finklestein A, West S, Svoboda K, Li N (2022). Activity maps of orofacial rhythms. Society for Neuroscience, San Diego CA, Poster.
We have started applying a novel experimental framework to examine circuit malfunctions in mouse models of neurological disorders. Using a newly developed home-cage system in our lab, self-motivated mice engage in cognitive and motor tasks over several months while we monitor the onset and progression of behavioral dysfunction as neuropathology appears and advances. Instead of cross-sectional analysis, we longitudinally track the progression in individual animals. We are further combining this approach with brain-wide analysis of neural activity using Neuropixels recordings and 2-photon imaging, and will use this platform to explore treatment options, such as deep brain stimulation.
Ki Y, Zoghbi H, Li N (2023). Home-cage assisted measurements of decision-making reveal deficits in Mecp2+/- mice. Society for Neuroscience, Washington, D.C., Poster.
Hao Y, Thomas AM, Li N, (2021). Fully autonomous mouse behavioral and optogenetic experiments in home-cage. eLife, 2021. https://doi.org/10.7554/eLife.66112
Li Publications
Reviews
Li N, Mrsic-Flogel TD, (2020). Cortico-cerebellar interactions during goal-directed behavior. Curr Opin Neurobiol. 23;65:27-37. https://doi.org/10.1016/j.conb.2020.08.010
Svoboda K, Li N (2017). Neural mechanisms of movement planning: motor cortex and beyond. Curr Opin Neurobiol. https://doi.org/10.1016/j.conb.2017.10.023
Selected Primary Papers
Kim, J.H., Daie, K., and Li, N. (2024). A combinatorial neural code for long-term motor memory. BioRxiv. https://doi.org/10.1101/2024.06.05.597627
Chen S*, Liu Y*, Wang Z, Colonell J, Liu LD, Hou H, Tien NW, Wang T, Harris T, Druckmann S #, Li N #, Svoboda K # (2024) Brain-wide neural activity underlying memory-guided movement. Cell 187(3):676-691. https://doi.org/10.1016/j.cell.2023.12.035
Thomas A*, Yang W*, Wang C, Tipparaju SL, Chen G, Sullivan B, Swiekatowski K, Tatam M, Gerfen C, Li N (2023). Superior colliculus bidirectionally modulates choice activity in frontal cortex. Nat Commun. 14(1):7358. https://doi.org/10.1038/s41467-023-43252-9
Zhu J, Hasanbegović H, Liu LD, Gao Z #, Li N #, (2023) Activity map of a cortico-cerebellar loop underlying motor planning. Nat. Neurosci. 26, 1916-1928. https://doi.org/10.1038/s41593-023-01453-x
Mangin E, Chen J, Lin J, Li N, (2023). Behavioral measurements of motor readiness in mice. Curr Biol 25, 1339-1352. https://doi.org/10.1016/j.cub.2023.07.029
Yang W, Tipparaju SL, Chen G, Li N, (2022). Orderly and thalamus-driven frontal cortex activity supports decision-making. Nat. Neurosci., 25, 1339-1352. https://doi.org/10.1038/s41593-022-01171-w
Liu LD, Chen S, Hou H, Faulkner M, International Brain Laboratory, Economo MN, Li N #, Svoboda K #, (2021). Accurate localization of linear probe electrode arrays across multiple brains. eNeuro. 8(6):ENEURO.0241-21.2021. https://doi.org/10.1523/ENEURO.0241-21.2021
Chen G, Kang B, Lindsey J, Druckmann S #, Li N #, (2021). Modularity and robustness of frontal cortex networks. Cell, 184(14):3717-3730. https://doi.org/10.1016/j.cell.2021.05.026
Hao Y, Thomas AM, Li N, (2021). Fully autonomous mouse behavioral and optogenetic experiments in home-cage. eLife, 2021. https://doi.org/10.7554/eLife.66112
Gao Z, Davis C, Thomas AM, Economo MN, Abrego AM, Svoboda K, De Zeeuw C, Li N (2018). A Cortico-cerebellar loop for motor planning. Nature 563(7729):113-116. https://doi.org/10.1038/s41586-018-0633-x
All Papers
Kim, J.H., Daie, K., and Li, N. (2024). A combinatorial neural code for long-term motor memory. BioRxiv. DOI: 10.1101/2024.06.05.597627. PMC11185691
Chen S*, Liu Y*, Wang Z, Colonell J, Liu LD, Hou H, Tien NW, Wang T, Harris T, Druckmann S #, Li N #, Svoboda K # (2024) Brain-wide neural activity underlying memory-guided movement. Cell 187(3):676-691.
Wang, Z.A., Chen, S., Liu, Y., Liu, D., Svoboda, K., Li, N., and Druckmann, S. (2023). Not everything, not everywhere, not all at once: a study of brain-wide encoding of movement. BioRxiv. DOI: 10.1101/2023.06.08.544257. PMC10274914
Thomas A*, Yang W*, Wang C, Tipparaju SL, Chen G, Sullivan B, Swiekatowski K, Tatam M, Gerfen C, Li N (2023). Superior colliculus bidirectionally modulates choice activity in frontal cortex. Nat Commun. 14(1):7358.
Zhu J, Hasanbegović H, Liu LD, Gao Z #, Li N #, (2023) Activity map of a cortico-cerebellar loop underlying motor planning. Nat. Neurosci. 26, 1916-1928.
Yang W, Tipparaju SL, Chen G, Li N, (2022). Orderly and thalamus-driven frontal cortex activity supports decision-making. Nat. Neurosci., 25, 1339-1352.
Inagaki HK, Chen S, Ridder MC, Sah P, Li N, Yang Z, Hasanbegovic H., Gao Z, Gerfen CR, Svoboda K, (2022). A midbrain - thalamus - cortex circuit reorganizes cortical dynamics to initiate planned movement. Cell, 185(6):1065-1081.
Liu LD, Chen S, Hou H, Faulkner M, International Brain Laboratory, Economo MN, Li N #, Svoboda K #, (2021). Accurate localization of linear probe electrode arrays across multiple brains. eNeuro. 8(6):ENEURO.0241-21.2021. doi: 10.1523/ENEURO.0241-21.2021.
Chen G, Kang B, Lindsey J, Druckmann S #, Li N #, (2021). Modularity and robustness of frontal cortex networks. Cell, 184(14):3717-3730.
Hao Y, Thomas AM, Li N, (2021). Fully autonomous mouse behavioral and optogenetic experiments in home-cage. eLife, 2021. May 4. doi: 10.7554/eLife.66112.
Finkelstein A, Fontolan L, Economo MN, Li N, Romani S, Svoboda K, (2021). Attractor dynamics gate cortical information flow during decision-making. Nat. Neurosci. doi: 10.1038/s41593-021-00840-6.
Mahrach A, Chen G, Li N, van Vreeswijk C, Hansel D (2020). Mechanisms underlying the response of mouse cortical networks to optogenetic manipulation. eLife. 2020 Jan 17;9. pii: e49967. doi: 10.7554/eLife.49967.
Li N#, Chen S, Guo ZV, Chen H, Huo Y, Inagaki HK, Chen C, Davis C, Hansel D, Guo C, Svoboda K#, (2019). Spatiotemporal constraints on optogenetic inactivation in cortical circuits. eLife. 2019 Nov 18;8. pii: e48622. doi: 10.7554/eLife.48622.
Gao Z, Davis C, Thomas AM, Economo MN, Abrego AM, Svoboda K, De Zeeuw C, Li N (2018). A Cortico-cerebellar loop for motor planning. Nature 563(7729):113-116.
Wei Z, Inagaki H, Li N, Svoboda K, and Druckmann S (2019). An orderly single-trial organization of population dynamics in premotor cortex predicts behavioral variability. Nat Commun, 10(1):216.
Chen TW, Li N, Daie K, Svoboda K, (2017). A Map of Anticipatory Activity in Mouse Motor Cortex. Neuron 94(4):866-879.
Li N*, Daie K*, Svoboda K, Druckmann S, (2016). Robust neuronal dynamics in premotor cortex during motor planning. Nature 532(7600):459-64.
Guo JZ, Graves AR, Guo WW, Zheng J, Lee A, Rodríguez-González J, Li N, Macklin JJ, Phillips JW, Mensh BD, Branson K, Hantman AW, (2015). Cortex commands the performance of skilled movement. eLife 4. pii: e10774.
Li N, Chen TW, Guo ZV, Gerfen CR, Svoboda K, (2015). A motor cortex circuit for motor planning and movement. Nature 519(7541):51-56.
Guo ZV*, Li N* , Huber D, Ophir E, Gutnisky D, Ting JT, Feng G, Svoboda K, (2014). Flow of cortical activity underlying a tactile decision in mice. Neuron 81(1):179-94. * equal contribution
Guo ZV, Hires SA, Li N, O’Connor DH, Komiyama T, Ophir E, Huber D, Bonardi C, Morandell K, Gutnisky D, Peron S , Xu NL, Cox J, Svoboda K, (2014). Procedures for behavioral experiments in head-fixed mice. PLoS ONE 9(2):e88678
O'Connor DH, Hires SA, Guo ZV, Li N, Yu J, Sun QQ, Huber D, Svoboda K, (2013). Neural coding during active somatosensation revealed using illusory touch. Nat. Neurosci. 16(7):958-65.
Li N, DiCarlo JJ, (2012). Neuronal learning of invariant object representation in the ventral visual stream is not dependent on reward. J Neurosci. 32(19):6611-20.
Li N, DiCarlo JJ, (2010). Unsupervised natural visual experience rapidly reshapes size invariant object representation in inferior temporal cortex. Neuron 67:1062-75.
Li N, Cox DD, Zoccolan D, DiCarlo JJ, (2009). What response properties do individual neurons need to underlie position and clutter “invariant” object recognition? J Neurophysiol. 102: 360-76.
Li N, DiCarlo JJ, (2008). Unsupervised natural experience rapidly alters invariant object representation in visual cortex. Science 321:1502-7.
Wei M, Li N, Newlands SD, Dickman JD, Angelaki DE, (2006). Deficits in visuospatial memory during head motion after labyrinthine lesion. J Neurophysiol. 96:1676-82.
Li N, Angelaki DE, (2005). Updating visual space during motion in depth. Neuron 48:149-58.
Li N, Wei M, Angelaki DE, (2005). Primate memory saccade amplitude after intervened motion depends on target distance. J Neurophysiol. 94:722-33.
Li Datasets & Resources
Progress in science is increasingly driven by sharing data. Our lab is a part of the Neurodata Without Borders (NWB) initiative that promotes data standardization in neurophysiology.
A tutorial on writing neurophysiology MATLAB data into NWB2.0
We attempt to make all data available soon after publication. We also publish scripts that demonstrate how to use the data. In some cases, scripts that generate figures in the papers are also published. The following datasets are currently available.
- Dataset from Li N, Chen TW, Guo ZV, Gerfen CR, Svoboda K, (2015). Nature 519(7541):51-56. alm-1 (anterior lateral motor cortex 1)
- Dataset from Li N, Daie K, Svoboda K, Druckmann S, (2016). Nature 532(7600):459-464. alm-3 (anterior lateral motor cortex 3)
- Dataset from Gao Z, Davis C, Thomas AM, Economo MN, Abrego AM, Svoboda K, De Zeeuw C, Li N, (2018). Nature 563(7729):113-116. alm-4 (anterior lateral motor cortex 4)
- Dataset from Gao Z, Davis C, Thomas AM, Economo MN, Abrego AM, Svoboda K, De Zeeuw C, Li N, (2018). Nature 563(7729):113-116.
- Matlab format: https://zenodo.org/records/6653158
- NWB format: https://zenodo.org/records/6647629;
- Dataset from Chen G, Kang B, Lindsey J, Druckmann S, Li N, (2021). Cell, 184(14):3717-3730.
- Matlab format: https://zenodo.org/records/6713616
- Dataset from Yang W, Tipparaju SL, Chen G, Li N, (2022). Nat Neurosci, 25, 1339-1352.
- Matlab format: https://zenodo.org/records/6846161
- Dataset from Zhu J, Hasanbegović H, Liu LD, Gao Z, Li N (2023). Nat. Neurosci. 26, 1916-1928.
- NWB format: https://dandiarchive.org/dandiset/000572?pos=4
- Dataset from MAP project: Chen S, Liu Y, Wang Z, Colonell J, Liu LD, Hou H, Tien NW, Wang T, Harris T, Druckmann S, Li N, Svoboda K (2024) Cell 187(3):676-691.
- NWB format: https://dandiarchive.org/dandiset/000363?pos=3
- Hardware design files and software from Hao Y, Thomas AM, Li N (2020). Elife, 2021. May 4. doi: 10.7554/eLife.66112.
Li Lab Open Positions
Interested in Joining Us?
We are always excited to consider talented applicants interested in joining our lab. We welcome inquiries from all potential Undergraduate Students, Graduate Students and Postdocs. We welcome people from diverse backgrounds, and we prioritize teaching and mentoring.
Postdoctoral Fellows: We are looking for candidates with background in one or more of the following areas: mouse behavior, electrophysiology, 2-photon imaging, transcriptomics, or computational neuroscience. Candidates with a strong quantitative background are generally preferred. Interested candidates should send their CV, a brief statement of research interests and goals, and the names and contact information of 3 references to Nuo Li at nuo.li@duke.edu.
Graduate Student: Prospective students should apply through the Duke Neurobiology Ph.D. program. We also accept students from other graduate programs such as BME or Cell Biology.
Undergraduate Student: Undergraduate research opportunities are available on an individual project basis. Undergraduate students are expected to work with a senior mentor in the group (graduate student or postdoc). Interested applicants are encouraged to look at ongoing project directions in the lab and email Dr. Li to inquire.
Staff: Positions, when available, will be posted.
We may have an opening for an engineer position to start in the Spring/Summer of 2025. Please contact Dr. Li if you would like to apply.