Research Interest
How does the brain maintain a balance between flexibility & stability?
Our brain is a dynamic circuit capable of making continuous adaptation to the external cues throughout life. After initial assembly and development, an adult brain becomes relatively stable to generate accountable and precise responses yet still maintains certain level of plasticity for learning & adaptation. To understand how neuroplasticity is regulated in the mouse visual cortex, a sensory system featuring both precision and learning capability, our lab applies in vivo imaging approaches, together with computational, physiological, and molecular manipulation, to identify the underlying circuit and cellular basis of visual cortical plasticity.
Our brain is a dynamic circuit capable of making continuous adaptation to the external cues throughout life. After initial assembly and development, an adult brain becomes relatively stable to generate accountable and precise responses yet still maintains certain level of plasticity for learning & adaptation. To understand how neuroplasticity is regulated in the mouse visual cortex, a sensory system featuring both precision and learning capability, our lab applies in vivo imaging approaches, together with computational, physiological, and molecular manipulation, to identify the underlying circuit and cellular basis of visual cortical plasticity.
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Current Projects |
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Neuromodulatory projections regulating visual plasticity
Growing evidence indicates that the brain works as a whole, relying on interaction of various factors in the local circuit as well as cross-talk between different brain regions. For example, visual cortical neurons in awake behaving animals not only respond to visual stimuli but also are modulated by animal’s behavioral states through neuromodulatory pathways. However, it remains unclear how visual cortex integrates sensory and non-sensory modulatory information from specific subcortical structures to regulate plasticity. To answer this question, we apply close-loop visual training, together with imaging, electrophysiology, and optogenetics, to dissect the contribution of individual neuromodulatory pathway in this process.
Growing evidence indicates that the brain works as a whole, relying on interaction of various factors in the local circuit as well as cross-talk between different brain regions. For example, visual cortical neurons in awake behaving animals not only respond to visual stimuli but also are modulated by animal’s behavioral states through neuromodulatory pathways. However, it remains unclear how visual cortex integrates sensory and non-sensory modulatory information from specific subcortical structures to regulate plasticity. To answer this question, we apply close-loop visual training, together with imaging, electrophysiology, and optogenetics, to dissect the contribution of individual neuromodulatory pathway in this process.
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Local cellular interaction involved in neuroplasticity
Although circuit plasticity is manifested in the activities of excitatory neurons, other local factors like interneurons and glial cells have been gradually recognized as critical players in modulating circuit changes. It was remains unclear how they change and influence excitatory neurons to achieve plasticity, due to technical challenges like sparsity, lack of spiking activity, and diverse subtype responses.
Our lab will address this question by taking advantage of genetic labelling, chronic 2-photon imaging, and dual-cell recordings to track the activity patterns of excitatory neurons and genetically labeled interneurons during visual plasticity to identify how specific subtypes of interneurons change their synaptic connectivity and alter the circuit. We will also employ inducible transgenic lines and pharmacological manipulation to examine other factors like glial cells and pericytes in the blood vessels.
Although circuit plasticity is manifested in the activities of excitatory neurons, other local factors like interneurons and glial cells have been gradually recognized as critical players in modulating circuit changes. It was remains unclear how they change and influence excitatory neurons to achieve plasticity, due to technical challenges like sparsity, lack of spiking activity, and diverse subtype responses.
Our lab will address this question by taking advantage of genetic labelling, chronic 2-photon imaging, and dual-cell recordings to track the activity patterns of excitatory neurons and genetically labeled interneurons during visual plasticity to identify how specific subtypes of interneurons change their synaptic connectivity and alter the circuit. We will also employ inducible transgenic lines and pharmacological manipulation to examine other factors like glial cells and pericytes in the blood vessels.
Promoting optical nerve regeneration using nanostructure and NIR light therapy
Limited ability of axonal regeneration in the mature nervous system results in low recovery rate and often functional loss following neurotraumatic injuries and neuropathies. The mature optic nerve in the adult brain cannot regenerate after damage, an ophthalmic condition commonly seen in glaucoma and one of the most common causes of blindness worldwide.
This project aims to verify the therapeutic effect and the underlying biological mechanisms of a designer bioactive nanostructure, VGF-derived TLQP-21 peptide amphiphile, in promoting adult neurogenesis. Recent studies identified that the VGF protein, a precursor polypeptide family induced by neurotrophic factors, plays an instructive role in neurogenesis in the adult brain. In collaboration with Northwestern University, we have generated VGF-derivative TLQP-21 peptide amphiphile (PA) nanostructures, which can be safely delivered to the brain and act as dynamic bioactive nanofibers to trigger neuronal repair in primary cell culture experiments.
Limited ability of axonal regeneration in the mature nervous system results in low recovery rate and often functional loss following neurotraumatic injuries and neuropathies. The mature optic nerve in the adult brain cannot regenerate after damage, an ophthalmic condition commonly seen in glaucoma and one of the most common causes of blindness worldwide.
This project aims to verify the therapeutic effect and the underlying biological mechanisms of a designer bioactive nanostructure, VGF-derived TLQP-21 peptide amphiphile, in promoting adult neurogenesis. Recent studies identified that the VGF protein, a precursor polypeptide family induced by neurotrophic factors, plays an instructive role in neurogenesis in the adult brain. In collaboration with Northwestern University, we have generated VGF-derivative TLQP-21 peptide amphiphile (PA) nanostructures, which can be safely delivered to the brain and act as dynamic bioactive nanofibers to trigger neuronal repair in primary cell culture experiments.
Driving cortical plasticity with electrical stimulation
Focal brain stimulation is a rapid-evolving neurotechnology recognized for its high efficacy in altering brain activities and treating neurological disorders. In particular, there is a growing interest in using intracortical microstimulation (ICMS) to develop neural prosthetics and aid neurorehabilitation. However, the cellular mechanisms by which ICMS works remain largely unexplored and its stimulating protocols are often set empirically, limiting the evaluation and optimization of effective ICMS interventions.
Our research is focused on the key cellular underpinnings of how ICMS drives visual enhancement and post-stroke recovery using rodent models. This research vision is built upon our recent work combining 2-photon microscopy and electrical stimulation in the awake mouse cortex for longitudinal quantification of the ICMS effects in the local brain area. By combining this multimodal platform with pharmacological and molecular toolkits, we will elucidate the biological processes in different types of brain cells that result from acute and chronic electrical stimulation, identifying biomarkers and key players underlying ICMS-driven brain plasticity and applying the generated knowledge in a stroke model to design effective ICMS therapies for post-injury rehabilitation.
Focal brain stimulation is a rapid-evolving neurotechnology recognized for its high efficacy in altering brain activities and treating neurological disorders. In particular, there is a growing interest in using intracortical microstimulation (ICMS) to develop neural prosthetics and aid neurorehabilitation. However, the cellular mechanisms by which ICMS works remain largely unexplored and its stimulating protocols are often set empirically, limiting the evaluation and optimization of effective ICMS interventions.
Our research is focused on the key cellular underpinnings of how ICMS drives visual enhancement and post-stroke recovery using rodent models. This research vision is built upon our recent work combining 2-photon microscopy and electrical stimulation in the awake mouse cortex for longitudinal quantification of the ICMS effects in the local brain area. By combining this multimodal platform with pharmacological and molecular toolkits, we will elucidate the biological processes in different types of brain cells that result from acute and chronic electrical stimulation, identifying biomarkers and key players underlying ICMS-driven brain plasticity and applying the generated knowledge in a stroke model to design effective ICMS therapies for post-injury rehabilitation.
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Collaborators |
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Dadarlat LabIbrahim LabLiu LabGuo Lab |
Biomedical Engineering, Purdue University, USABiosciences, KAUST, Saudi ArabiaNeurological Surgery, UCSF, USA
School of Electrical Engineering, Wuhan University, China |
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Funding sources |
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