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Leon Levy Fellows in Neuroscience Fifth Annual Symposium May 4, 2016

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Leon Levy Fellows in Neuroscience Fifth Annual Symposium May 4, 2016 LEON LEVY FELLOWS IN NEUROSCIENCE FIFTH ANNUAL SYMPOSIUM MAY 4, 2016 ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI LEON LEVY FELLOWSHIP PROGRAM The Leon Levy Foundation (LLF) continues to advance Leon Levy’s interest in neuroscience by identifying and supporting the most exceptional individuals as they begin their research careers in studies of the mind, brain, and behavior. The founda- tion decided to pursue this core interest by establishing Leon Levy Fellowships in neuroscience at select New York institutions. Our goal is to advance the careers of the most outstanding young neuroscientists and to encourage them to pursue YPZR[HRPUNYLZLHYJOPKLHZ[OH[^V\SKUV[ÄUKZ\WWVY[MYVTV[OLYZV\YJLZ Our interest is in fundamental research to increase our understanding of the brain with particular emphasis on the relationship between brain function and its impact on human behavior. Although the LLF will not fund clinical trials, diseases of the brain- particularly those that affect behavior- are of interest to the foundation. All fellowship WYVNYHTHMÄSPH[LZILULÄ[MYVTWHY[PJPWH[PVUPUV\YHUU\HSZ`TWVZP\T^OPJOPZ intended to foster connections and collaborations between researchers and across We hope institutions. you will Our hope is that these neuroscientists, along with their mentors, will raise the level of neuroscience research in New York and throughout the world. join us in The Overarching Goals of the 2017 for Leon Levy Fellowship in Neuroscience Program the Sixth t5PTVQQPSUBOEOVSUVSFFYDFQUJPOBMZPVOHSFTFBSDIFSTJOUIFöFME t5PTVQQPSUUIFTFSFTFBSDIFSTJOUIFJSQVSTVJUPGJOOPWBUJWF SJTLUBLJOH JOWFTUJHBUJPOT Annual t5PTVQQPSUSFTFBSDIUIBUXJMMNBLFBNFBOJOHGVMDPOUSJCVUJPOUPPVS VOEFSTUBOEJOHJOUIFCBTJDBOEDMJOJDBMOFVSPTDJFODFT t5PIFMQUIFCFTUZPVOHSFTFBSDIFSTBEWBODFUIFJSDBSFFSTUPXBSE Symposium JOEFQFOEFOUSFTFBSDI t5PQSPNPUFTZOFSHJFTBOEDPMMBCPSBUJPOTBNPOHJOEJWJEVBMTBDSPTT UIFHSBOUFFJOTUJUVUJPOT t5PVTF--'HSBOUGVOETBTFóDJFOUMZBTQPTTJCMF t5PDSFBUFBöUUJOHMFHBDZUPIPOPS-FPO-FWZTJOUFSFTUJOOFVSPTDJFODF Leon Levy had a passion for expanding knowledge and believed in the power of PKLHZHUKHQ\Z[HUKLX\P[HISLZVJPL[`;OPZIYVHKO\THUPZTHSZVKLÄULKOPZ philanthropy. ;OL33-MV\UKLKPUPZHWYP]H[LUV[MVYWYVÄ[MV\UKH[PVUJYLH[LKMYVTOPZ estate. The foundation endeavors to continue Leon Levy’s philanthropic legacy and to build on his vision, encouraging and supporting excellence in six broad areas: Understanding the Ancient World; Arts and Humanities; Preservation of Nature and Gardens; Neuroscience Research; Human Rights; and Jewish Culture. SCIENCE FOR THE BENEFIT OF HUMANITY DEAR FRIENDS, 3LVU3L]`^HZHIYPSSPHU[ÄUHUJPLYVU>HSS:[YLL[I\[PUJVSSLNLOLTHQVYLK PUWZ`JOVSVN`UV[LJVUVTPJZ/LOHKHJ\YPVZP[`HIV\[^O`WLVWSLHJ[LK HZ[OL`KPK(ZHUPU]LZ[VYOLZHPK¸PU[\P[PVUHUKHUHS`ZPZHYLPUL_[YPJHIS` IV\UK[VNL[OLY¹6ULULLKLKHUPKLHI\[[OLUVULULLKLK[VKV[OL YLZLHYJO^OPJOPUMHJ[PZHSZV[Y\LVM[OLZJPLU[PÄJWYVJLZZ;OPZSLK[VOPZ PU[LYLZ[PUUL\YVZJPLUJLHZH^H`VMSLHYUPUNTVYLHIV\[OV^[OLIYHPU M\UJ[PVUZHUKPTWHJ[ZILOH]PVY0[PZUV[HJVPUJPKLUJL[OH[OL^YV[LH IVVRLU[P[SLK;OL4PUKVM>HSS:[YLL[ /LLUNHNLKPUKPZJ\ZZPVUZ^P[OLTPULU[ZJPLU[PZ[ZZ\JOHZ;VYZ[LU>PLZLS HUK7H\S.YLLUNHYKHTVUNV[OLYZHIV\[UL^KL]LSVWTLU[ZPUUL\YVZJP- LUJL;OPZSLK[VOPZKLJPZPVU[VJYLH[L;OL:OLSI`>OP[LHUK3LVU3L]` *LU[LYMVY4PUK)YHPUHUK)LOH]PVYH[9VJRLMLSSLY<UP]LYZP[`^P[O;VYZ[LU HZP[ZÄYZ[KPYLJ[VY /L^V\SKOH]LILLUKLSPNO[LK[OH[^P[O[OL-V\UKH[PVU»ZZ\WWVY[`V\UN YLZLHYJOLYZHYLMYLL[V\UKLY[HRLJ\[[PUNLKNLYLZLHYJO/L^V\SKOH]L LUQV`LKTLL[PUN[OL3LVU3L]`-LSSV^ZPU[OLPYSHIVYH[VYPLZHUKH[[OLZL Z`TWVZP\TZ[VKPZJV]LYTVYLHIV\[[OLPY^VYR >L[OHUR+Y,YPJ5LZ[SLYMVYOVZ[PUNV\Y-PM[O(UU\HS:`TWVZP\TOLYLH[ 0JHOU:JOVVSVM4LKPJPULH[4V\U[:PUHP :OLSI`>OP[L -V\UKPUN;Y\Z[LL 3LVU3L]`-V\UKH[PVU SESSION ONE REGISTRATION and BOX LUNCH Davis Auditorium, Hess Building 11:45 – 12:30 p.m. 1470 Madison Avenue (between 101st & 102nd), 2nd Floor INTRODUCTION and WELCOMING REMARKS Eric Nestler, MD, PhD 12:30 p.m. Nash Family Professor +LHUMVY(JHKLTPJHUK:JPLU[PÄJ(MMHPYZ Director, Friedman Brain Institute Icahn School of Medicine at Mount Sinai Yasmin Hurd, PhD (Symposium Emcee) Professor, Department of Psychiatry and Neuroscience Director of the Center for Addictive Disorders Icahn School of Medicine at Mount Sinai LEON LEVY FELLOWS 12:40 p.m. Atheir Abbas, MD, PhD Columbia University Medical Center The role of prefrontal interneuron subtypes in working memory Introduction by Joshua Gordon, MD, PhD Jayeeta Basu, PhD 1:20 p.m. NYU Langone Medical Center Reciprocal interactions between the hippocampus and entorhinal cortex memory circuit Introduction by György Buzsáki, MD, PhD Sam Horng, MD, PhD 2:00 p.m. Icahn School of Medicine at Mount Sinai Claudin-4 is required for astrocytic tight junction MVYTH[PVUHUKWYV[LJ[ZHNHPUZ[PUÅHTTH[VY`SLZPVU size and severity in the central nervous system Introduction by Gareth John, MD, PhD COFFEE BREAK COFFEE BREAK 2:40 p.m. SESSION TWO LEON LEVY FELLOWS Dilek Colak, PhD 3:10 p.m. Weill Cornell Medicine The role of local RNA degradation in synaptic plasticity and cognitive function Introduction by M. Elizabeth Ross, MD, PhD Nicolas Renier, PhD 3:50 p.m. The Rockefeller University Complete mapping of cellular brain activity and axonal projections by tissue clearing and automated volume analysis Introduction by Cori Bargmann, PhD REMARKS 4:35 p.m. Shelby White Founding Trustee Leon Levy Foundation PLENARY TALK 4:45 p.m. Pamela Sklar, MD, PhD ory Chief, Division of Psychiatric Genomics Department of Psychiatry Professor of Psychiatry, Neuroscience, Genetics and Genomics Icahn School of Medicine at Mount Sinai Using genomics to change our understanding of mental illness RECEPTION and POSTER SESSION RECEPTION and POSTER SESSION 5:30 – 7:00 p.m. LEON LEVY FELLOWS Speaker Abstracts Atheir Abbas, MD, PhD Jayeeta Basu, PhD Columbia University Medical Center NYU Langone Medical Center The role of prefrontal interneuron sub- Reciprocal interactions between the types in working memory hippocampus and entorhinal cortex memory circuit Schizophrenia has previously been hypothesized to result from synaptic disease that leads to failure of Our research examines the dynamic interactions functional integration in the brain – “a disconnection between the hippocampus and the entorhinal cortex in syndrome.” Accumulating evidence supports this the mouse to understand sensory integration and the view, though the cellular mediators of connectivity formation of long-term memories. Learning and memory formation are necessary for our sense of self within the brain are not well understood. Given data and individuality. These brain functions are crucial in showing that two classes of inhibitory neurons, parval- our ability to adapt to changing environments and alter bumin and somatostatin interneurons, are abnormal in behavior in a contextually appropriate manner. individuals with schizophrenia, I hypothesize that prefrontal cortical interneurons support working The entorhinal cortex routes sensory and associational memory by maintaining connectivity. To test this inputs from many brain regions to the hippocampus for hypothesis, I selectively silenced prefrontal parvalbu- mnemonic processing. Despite a great deal of min and somatostatin interneurons in mice during research into how excitatory inputs from entorhinal performance of a spatial working memory task while cortex regulate hippocampal dependent activity, learning and memory, little is known about the role of simultaneously recording brain activity in the prefrontal long-range inhibitory connections between these cortex and other brain areas known to be involved in HYLHZ0^PSSÄYZ[WYLZLU[YLZ\S[ZVMHYLJLU[S`W\ISPZOLK working memory. I have found that silencing soma- study (Basu et al., Science 2016), where we have tostatin interneurons is associated with an impairment functionally characterized a ‘disinhibitory’ GABAergic in both connectivity and spatial working memory. long-range projection circuit from the lateral entorhinal Silencing parvalbumin interneurons has no effect on JVY[L_[V[OLOPWWVJHTW\Z>LÄUK[OH[[OLZLPUW\[Z LP[OLYJVUULJ[P]P[`VY^VYRPUNTLTVY`;OLZLÄUKPUNZ gate dendritic spikes and induce long-term plasticity suggest that interneuron dysfunction may contribute to by suppressing local feed-forward inhibition. Using JVNUP[P]LKLÄJP[ZPUZJOPaVWOYLUPH two-photon imaging and genetic silencing approaches in vivo during sensory experiences and learning behav- ior, we found that the GABAergic projections are important for contextual and object recognition memory. Next, I will present exciting preliminary data describing the functional connectivity of the largely unexplored feed-back projection circuit from the hippocampus to the entorhinal cortex. Does the hippocampus modu- late the integration of sensory information in the entorhinal cortex, thereby providing a mechanism for previous memories seated within the hippocampus to shape the future processing of new experiences? Speaker Abstracts Sam Horng, MD, PhD Icahn School of Medicine at Mount Sinai Claudin-4 is required for astrocytic tight junction formation and protects against LQñDPPDWRU\ OHVLRQ VL]H DQG VHYHULW\ LQ WKHFHQWUDOQHUYRXVV\VWHP Background: A protective barrier restricts the passage of lymphocytes and soluble proteins from the blood- stream into the CNS parenchyma. Termed the blood brain barrier, this structure was traditionally character- ized as a single layer of tight-junction bonds between CNS blood vessel cells. Recent work has revealed that eliminating a layer of supportive cells called astro- cytes, which encircles the endothelial blood brain IHYYPLYL_HJLYIH[LZSLZPVUZPaLHUKZL]LYP[`PUPUÅHT- matory conditions of the CNS. We hypothesized
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