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506    <div class="min-w-0 min-h-0 max-w-full text-content">
507      <div class="text-m-research pt-8 pb-12">
508    Our lab’s research focuses on elucidating how memory is encoded, retained, and retrieved within
509    neural networks and molecules in the brain. We employ and develop cutting-edge tools to record
510    and manipulate neuronal and molecular activities to unravel neural mechanisms underlying
511    memory processes. Our integrative approach combines electrophysiology, imaging, behavior,
512    genetic manipulations, omics, and computational modeling.
513    <br>
514    <br>
515    The major tools used in the lab include <em>in vivo</em> electrophysiology, two-photon calcium imaging,
516    one-photon endoscopic imaging, fiber photometry, opto-/chemo-genetic manipulations, and <em>ex
517    vivo</em> electrophysiology. We also actively develop our own tools to address specific scientific
518    questions through bioengineering, chemical synthesis, (nano)materials engineering, and
519    electrical engineering.
520</div>
521<div class="flex lg:grid-cols-2 justify-between py-2 pt-12">
522    <div class="flex self-end text-research-title text-primary-500" style="width: 24rem">
523        Elucidating neural networks supporting memory encoding and consolidation
524    </div>
525    <div class="self-end text-subtitle italic" style="width: 54rem">
526        <u><a href="https://www.nature.com/articles/s41586-020-2771-1" class="text-neutral-900">See</a></u> how we identified a hypothalamic novelty hub and how it modulates different types of memories in the hippocampus.
527    </div>
528</div>
529<div class="border-b-1 pt-2"></div>
530<div class="text-m-research pb-2 pt-6">
531    Much of our work focuses on the hippocampus, a brain region giving rise to neural sequences
532    underlying episodic memory. These sequences, occurring during both behavior (e.g. theta
533    sequences) and sleep (e.g. replay sequences), lay the foundation for memory encoding and
534    consolidation. We believe what drives these sequences is a brain-wide oscillation network, and
535    our lab is elucidating the key nodes in this network and how information is transmitted and
536    computed among them.
537    <br>
538    <div class="pt-2"></div>
539    One recent focus of the lab is an understudied subcortical structure in the brain’s oscillation
540    network, the supramammillary nucleus (SuM). This small hypothalamic nucleus is unique in its
541    broad, extensive connections to the hippocampus and cortex. We are investigating how these
542    long-range, bottom-up pathways modulate network dynamics to process memory.
543</div>
544<div class="pt-4"></div>
545<div class="not-prose lg:grid-research-elucidating mx-auto article_content lg:max-w-full py-2">
546    <div class="grid-img-subtitle h-full">
547        <div class="flex justify-center">
548            <video class="video-shortcode" preload="auto" autoplay="false" width="100%" height="" controls loop>
549                <source src="/img/research/elucidating_1.mp4" type="video/mp4">
550                There should have been a video here but your browser does not seem
551                to support it.
552            </video>
553
554        </div>
555        <div class="self-start text-subtitle">Whole-brain mapping of SuM projections by clearing.</div>
556    </div>
557    <div class="grid-img-subtitle h-full">
558        <div class="flex justify-center"><img src="/img/research/elucidating_2.png" class="h-full"></div>
559        <div class="self-start text-subtitle">SuM soma (top) and axons in the hippocampus (bottom).</div>
560    </div>
561    <div class="grid-img-subtitle h-full">
562        <div class="flex self-center">
563            <img src="/img/research/elucidating_3.jpg">
564        </div>
565        <div class="self-start text-subtitle">
566            Optogenetic identification and recording of DG- (top) and CA2-(bottom) projecting SuM neurons during behavior.
567        </div>
568    </div>
569</div>
570<div class="text-m-research pb-16"></div>
571<div class="flex lg:grid-cols-2 justify-between py-2 pt-12">
572    <div class="self-center text-research-title text-primary-500" style="width: 24rem">
573        Deciphering neural computation underlying memory-guided behavior
574    </div>
575</div>
576<div class="border-b-1 pt-2"></div>
577<div class="text-m-research pb-2 pt-6">
578    Complex cognitive activities, such as thinking and planning, rely on established knowledge
579    about the external world. We believe that through elaborately designed behavioral tasks
580    combined with large-scale <em>in vivo</em> recordings of neural activity, we may probe the underlying
581    neural computation mechanisms.
582    <br>
583    <div class="pt-2"></div>
584    Our lab employs this approach to investigate how the brain synthesizes novel ideas and solutions
585    from stored information–i.e. memory retrieval and utilization. By drawing inspiration from
586    psychology, engineering, and computer sciences, we aim to dissect neural computational
587    mechanisms underlying memory-guided complex behaviors.
588</div>
589<div class="pt-2"></div>
590<div class="flex not-prose grid py-2 gap-2">
591    <div class="self-start max-w-35" style="aspect-ratio: 9 / 8">
592        <video class="video-shortcode" preload="auto" autoplay="false" width="100%" height="100%" controls loop>
593            <source src="/img/research/deciphering_1.mp4" type="video/mp4">
594            There should have been a video here but your browser does not seem
595            to support it.
596        </video>
597
598    </div>
599    <div class="self-start text-subtitle">
600        Goal-directed spatial navigation in T-maze.
601    </div>
602</div>
603<div class="text-m-research pb-8"></div>
604<div class="flex lg:grid-cols-2 justify-between py-2 pt-12">
605    <div class="self-center text-research-title text-primary-500" style="width: 24rem">
606        Developing next-generation, noninvasive brain machine interfaces for memory and cognitive control
607    </div>
608    <div class="self-end text-subtitle italic" style="width: 54rem">
609        <u><a href="https://www.science.org/doi/full/10.1126/science.aaq1144" class="text-neutral-900">See</a></u> 
610        how we developed and showcased a minimally invasive technology, 
611        near-infrared upconversion optogenetics, for various neuromodulation applications, 
612        e.g. recalling an episodic memory by transcranial NIR light.
613    </div>
614</div>
615<div class="border-b-1 pt-2"></div>
616<div class="text-m-research pb-2 pt-6">
617    Manipulating memory and cognition requires technologies to spatiotemporally modulate nervous
618    systems in deep tissue, sometimes in a precision closed-loop manner. For decades, physicians
619    have utilized implanted electrodes connected through wires to a pacemaker-like device under the
620    skin of the chest to electrically stimulate neurons deep in the brain. This approach, known as
621    deep brain stimulation, has proven to be effective, but is costly, highly invasive, and lacks cell
622    specificity.
623    <br>
624    <div class="pt-2"></div>
625    Our lab is developing noninvasive, high-precision neuromodulation technologies to manipulate
626    diverse deep structures in the nervous system that are conventionally hard and intrusive to reach.
627    We adopt a cross-disciplinary approach by designing and synthesizing molecularly engineered,
628    noninvasively delivered nano- or micro-interfaces capable of converting tissue-penetrable stimuli
629    into signals recognized/sensible by genetically defined cells. We believe such efforts will
630    contribute to the field’s collective efforts in unlocking diverse routes towards next-generation,
631    noninvasive neuromodulation therapies.
632</div>
633<div class="pt-4"></div>
634<div class="not-prose lg:grid-research-developing mx-auto article_content lg:max-w-full py-2">
635    <div class="grid-img-subtitle h-full">
636        <div class="flex justify-center"><img src="/img/research/developing_1.png" class="h-full"></div>
637        <div class="self-start text-subtitle"> Near-infrared optogenetics mediated by upconversion nanoparticles (UCNPs).</div>
638    </div>
639    <div class="grid-img-subtitle h-full">
640        <div class="flex justify-center"><img src="/img/research/developing_2.png" class="h-full w-full"></div>
641        <div class="self-start text-subtitle">
642            Electron micrographs of UCNPs distributed in tissue (top). Reactivation of hippocampal engram (green) by UCNPs (blue).
643        </div>
644    </div>
645    <div class="grid-img-subtitle h-full">
646        <div class="flex justify-center">
647            <video class="video-shortcode" preload="auto" autoplay="false" width="100%" height="100%" controls loop>
648                <source src="/img/research/developing_3.mp4" type="video/mp4">
649                There should have been a video here but your browser does not seem
650                to support it.
651            </video>
652
653        </div>
654        <div class="self-start text-subtitle">
655            Real-time imaging of retrograde axonal transport of UCNPs under a total internal reflection fluorescence (TIRF) microscope.
656        </div>
657    </div>
658</div>
659<div class="text-m-research pb-8"></div>
660<div class="flex lg:grid-cols-2 justify-between py-2 pt-12">
661    <div class="flex items-center text-research-title text-primary-500" style="width: 24rem">
662        Linking molecular and network pathologies of Alzheimer’s disease
663    </div>
664    <div class="self-end text-subtitle italic" style="width:54rem">
665        <u><a href="https://alz.confex.com/alz/2024/meetingapp.cgi/Paper/93081" class="text-neutral-900">See</a></u> how we demonstrated the efficacy of a peptide drug that rescues synaptic 
666        function and cognitive function in a mouse model of advanced-stage AD.
667    </div>
668</div>
669<div class="border-b-1 pt-2"></div>
670<div class="text-m-research pb-2 pt-6">
671    Alzheimer&#39;s disease (AD) is the most prevalent cause of dementia in the elderly. There is
672    currently no cure for AD, and clinical trials only provide modest benefits.
673    <br>
674    <div class="pt-2"></div>
675    While characterized by pathological molecules like amyloid-β, tau and APOE4, AD is a mental
676    and cognitive disorder. How the molecular pathologies of AD lead to cognitive decline remains
677    elusive. Bridging this gap requires understanding neural circuit mechanisms. By leveraging our
678    expertise in systems neuroscience, our lab is identifying circuit pathophysiology of AD by using
679    animal models of different pathologies.
680    <br>
681    <div class="pt-2"></div>
682    Once elucidated, circuit mechanisms of AD could be employed to develop next-generation,
683    circuit-targeted therapies to restore memory and cognition. Individualized, circuit-oriented
684    diagnosis and treatment may become possible with time.
685</div>
686<div class="pt-4"></div>
687<div class="not-prose grid-linking mx-auto lg:max-w-full py-2">
688    <div class="grid-img-subtitle-lg">
689        <div class="h-full">
690            <video class="video-shortcode" preload="auto" autoplay="false" width="100%" height="100%" controls loop>
691                <source src="/img/research/linking_1.mp4" type="video/mp4">
692                There should have been a video here but your browser does not seem
693                to support it.
694            </video>
695
696        </div>
697        <div class="self-start text-subtitle">
698             <em>In vivo</em> calcium imaging using a head-mounted endoscope to probe hippocampal neural dynamics in the AD brain.
699        </div>
700    </div>
701    <div class="grid-img-subtitle-lg">
702        <div class="h-full flex gap-4 w-full">
703            <img src="/img/research/linking_2.png" class="h-full flex-1 min-w-0 object-contain">
704        </div>
705        <div>
706            <div class="self-start text-subtitle w-full">
707                <em>In vitro</em> electrophysiology to measure drug-modified synaptic plasticity.
708            </div>
709        </div>
710    </div>
711    <div class="grid-img-subtitle-lg">
712        <div class="h-full flex gap-4 w-full">
713            <img src="/img/research/linking_3.jpg" class="h-full flex-1 min-w-0 object-contain">
714        </div>
715        <div>
716            <div class="self-start text-subtitle w-full">
717                Laser capture microdissection of CA1 cell bodies for localized proteomics.
718            </div>
719        </div>
720    </div>
721</div>
722
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