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502<script type="text/javascript" src="/js/page.min.b06a29d42a4ed16787978e2eee1e8c797b7698db2bc14ccee78f5c80ac566fc996190a73ad80a5e987558474b20b96fa38f7d85b405f165ff72b7b163c5ad11b.js" integrity="sha512-sGop1CpO0WeHl44u7h6MeXt2mNsrwUzO549cgKxWb8mWGQpzrYCl6YdVhHSyC5b6OPfYW0BfFl/3K3sWPFrRGw=="></script>
502 503 </header> 504 <section class="mt-0 prose flex justify-center max-w-full flex-col dark:prose-invert lg:flex-row"> 505 506 <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 labâs 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 brainâs 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 informationâi.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 fieldâs 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 Alzheimerâs 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'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> 722 723 </div> 724 725 726 727 728 </section> 729 730 731 732 733 734 <div id="top-scroller" class="pointer-events-none absolute top-[110vh] bottom-0 w-12 ltr:right-0 rtl:left-0"> 735 <a href="#the-top" 736 class="pointer-events-auto sticky top-[calc(100vh-5.5rem)] flex h-12 w-12 mb-16 items-center justify-center rounded-full bg-neutral/50 text-xl text-neutral-700 hover:text-primary-600 dark:bg-neutral-800/50 dark:text-neutral dark:hover:text-primary-400" 737 aria-label="Scroll to top" title="Scroll to top"> 738 ↑ 739 </a> 740</div> 741 </main><footer id="site-footer" class="py-10 print:hidden"> 742 743 744 745 746 747 748 749 <div class="footer bg-neutral-200 py-2"> 750 <div class="flex items-start max-w-page mx-auto px-6 sm:px-14 md:px-24 lg:px-32"> 751 752 753 <div class="flex items-center"> 754 <img src="/img/nki_logo.png" alt="The Nathan S. Kline Institute for Psychiatric Research" class="h-10 pr-2"/> 755 </div> 756 <div class="self-center text-footer w-footer-name text-neutral-500" style="margin-right:1rem"> 757 The Nathan S. Kline Institute for Psychiatric Research 758 </div> 759 760 761 <div class="flex items-center"> 762 <img src="/img/langone_logo.png" alt="New York University Grossman School of Medicine" class="h-10 pr-2"/> 763 </div>
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