Honors & Awards

  • School of Medicine Dean's Postdoctoral Fellowship, Stanford University (2021-2022)
  • Career Advacement Award, Gladstone Institutes (2019)
  • F31 Predoctoral Fellowship, National Institute of Aging (2018-2019)
  • Genentech Foundation Fellowship, Genentech Foundation (2017-2018)
  • Graduate Student of the Year, Gladstone Institute of Neurological Disease (2017)
  • Young Scientist Award, Alzheimer's Association (2017)
  • Discovery Fellowship, UCSF (2016-2019)
  • Graduate Research Fellowship, National Science Foundation (2014-2017)

Boards, Advisory Committees, Professional Organizations

  • Chair, Gordon Research Seminar in Inhibition in the CNS (2019 - Present)

Professional Education

  • PhD, University of California, San Francisco, Biomedical Sciences (2019)
  • BS, University of Maryland, College Park, Computer Science (2014)
  • BS, University of Maryland, College Park, Biological Sciences: Physiology & Neurobiology (2014)

Stanford Advisors

Lab Affiliations

All Publications

  • Dentate Gyrus and CA3 GABAergic Interneurons Bidirectionally Modulate Signatures of Internal and External Drive to CA1 bioRxiv Aery Jones, E. A., Rao, A., Zilberter, M., Djukic, B., Gillespie, A. K., Koutsodendris, N., Nelson, M., Yoon, S., Huang, K., Yuan, H., Gill, T. M., Huang, Y., Frank, L. M. 2021
  • In Vivo Chimeric Alzheimer's Disease Modeling of Apolipoprotein E4 Toxicity in Human Neurons. Cell reports Najm, R., Zalocusky, K. A., Zilberter, M., Yoon, S. Y., Hao, Y., Koutsodendris, N., Nelson, M., Rao, A., Taubes, A., Jones, E. A., Huang, Y. 2020; 32 (4): 107962


    Despite its clear impact on Alzheimer's disease (AD) risk, apolipoprotein (apo) E4's contributions to AD etiology remain poorly understood. Progress in answering this and other questions in AD research has been limited by an inability to model human-specific phenotypes in an in vivo environment. Here we transplant human induced pluripotent stem cell (hiPSC)-derived neurons carrying normal apoE3 or pathogenic apoE4 into human apoE3 or apoE4 knockin mouse hippocampi, enabling us to disentangle the effects of apoE4 produced in human neurons and in the brain environment. Using single-nucleus RNA sequencing (snRNA-seq), we identify key transcriptional changes specific to human neuron subtypes in response to endogenous or exogenous apoE4. We also find that Aβ from transplanted human neurons forms plaque-like aggregates, with differences in localization and interaction with microglia depending on the transplant and host apoE genotype. These findings highlight the power of in vivo chimeric disease modeling for studying AD.

    View details for DOI 10.1016/j.celrep.2020.107962

    View details for PubMedID 32726626

    View details for PubMedCentralID PMC7430173

  • Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer's disease. Molecular neurodegeneration Najm, R. n., Jones, E. A., Huang, Y. n. 2019; 14 (1): 24


    Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD), increasing risk and decreasing age of disease onset. Many studies have demonstrated the detrimental effects of apoE4 in varying cellular contexts. However, the underlying mechanisms explaining how apoE4 leads to cognitive decline are not fully understood. Recently, the combination of human induced pluripotent stem cell (hiPSC) modeling of neurological diseases in vitro and electrophysiological studies in vivo have begun to unravel the intersection between apoE4, neuronal subtype dysfunction or loss, subsequent network deficits, and eventual cognitive decline. In this review, we provide an overview of the literature describing apoE4's detrimental effects in the central nervous system (CNS), specifically focusing on its contribution to neuronal subtype dysfunction or loss. We focus on γ-aminobutyric acid (GABA)-expressing interneurons in the hippocampus, which are selectively vulnerable to apoE4-mediated neurotoxicity. Additionally, we discuss the importance of the GABAergic inhibitory network to proper cognitive function and how dysfunction of this network manifests in AD. Finally, we examine how apoE4-mediated GABAergic interneuron loss can lead to inhibitory network deficits and how this deficit results in cognitive decline. We propose the following working model: Aging and/or stress induces neuronal expression of apoE. GABAergic interneurons are selectively vulnerable to intracellularly produced apoE4, through a tau dependent mechanism, which leads to their dysfunction and eventual death. In turn, GABAergic interneuron loss causes hyperexcitability and dysregulation of neural networks in the hippocampus and cortex. This dysfunction results in learning, memory, and other cognitive deficits that are the central features of AD.

    View details for DOI 10.1186/s13024-019-0324-6

    View details for PubMedID 31186040

    View details for PubMedCentralID PMC6558779

  • Early Hippocampal Sharp-Wave Ripple Deficits Predict Later Learning and Memory Impairments in an Alzheimer's Disease Mouse Model. Cell reports Jones, E. A., Gillespie, A. K., Yoon, S. Y., Frank, L. M., Huang, Y. n. 2019; 29 (8): 2123–33.e4


    Alzheimer's disease (AD) is characterized by progressive memory loss, and there is a pressing need to identify early pathophysiological alterations that predict subsequent memory impairment. Hippocampal sharp-wave ripples (SWRs)-electrophysiological signatures of memory reactivation in the hippocampus-are a compelling candidate for this purpose. Mouse models of AD show reductions in both SWR abundance and associated slow gamma (SG) power during aging, but these alterations have yet to be directly linked to memory impairments. In aged apolipoprotein E4 knockin (apoE4-KI) mice-a model of the major genetic risk factor for AD-we find that reduced SWR abundance and associated CA3 SG power predicted spatial memory impairments measured 1-2 months later. Importantly, SWR-associated CA3 SG power reduction in young apoE4-KI mice also predicted spatial memory deficits measured 10 months later. These results establish features of SWRs as potential functional biomarkers of memory impairment in AD.

    View details for DOI 10.1016/j.celrep.2019.10.056

    View details for PubMedID 31747587

  • Approaching Alzheimer's disease from a network level. Oncotarget Gillespie, A. K., Jones, E. A., Huang, Y. n. 2017; 8 (6): 9003–4

    View details for DOI 10.18632/oncotarget.14617

    View details for PubMedID 28099927

    View details for PubMedCentralID PMC5354704

  • Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples. Neuron Gillespie, A. K., Jones, E. A., Lin, Y. H., Karlsson, M. P., Kay, K. n., Yoon, S. Y., Tong, L. M., Nova, P. n., Carr, J. S., Frank, L. M., Huang, Y. n. 2016; 90 (4): 740–51


    Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD), but the mechanism by which it causes cognitive decline is unclear. In knockin (KI) mice, human apoE4 causes age-dependent learning and memory impairments and degeneration of GABAergic interneurons in the hippocampal dentate gyrus. Here we report two functional apoE4-KI phenotypes involving sharp-wave ripples (SWRs), hippocampal network events critical for memory processes. Aged apoE4-KI mice had fewer SWRs than apoE3-KI mice and significantly reduced slow gamma activity during SWRs. Elimination of apoE4 in GABAergic interneurons, which prevents learning and memory impairments, rescued SWR-associated slow gamma activity but not SWR abundance in aged mice. SWR abundance was reduced similarly in young and aged apoE4-KI mice; however, the full SWR-associated slow gamma deficit emerged only in aged apoE4-KI mice. These results suggest that progressive decline of interneuron-enabled slow gamma activity during SWRs critically contributes to apoE4-mediated learning and memory impairments. VIDEO ABSTRACT.

    View details for DOI 10.1016/j.neuron.2016.04.009

    View details for PubMedID 27161522

    View details for PubMedCentralID PMC5097044

  • Prenatal Nicotine Exposure Impairs Executive Control Signals in Medial Prefrontal Cortex. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Bryden, D. W., Burton, A. C., Barnett, B. R., Cohen, V. J., Hearn, T. N., Jones, E. A., Kariyil, R. J., Kunin, A. n., Kwak, S. I., Lee, J. n., Lubinski, B. L., Rao, G. K., Zhan, A. n., Roesch, M. R. 2016; 41 (3): 716–25


    Prenatal nicotine exposure (PNE) is linked to numerous psychiatric disorders including attention deficit hyperactivity disorder (ADHD). Current literature suggests that core deficits observed in ADHD reflect abnormal inhibitory control governed by the prefrontal cortex. Yet, it is unclear how neural activity in the medial prefrontal cortex (mPFC) is modulated during tasks that assess response inhibition or if these neural correlates, along with behavior, are affected by PNE. To address this issue, we recorded from single mPFC neurons in control and PNE rats as they performed a stop-signal task. We found that PNE rats were faster for all trial-types, made more premature responses, and were less likely to inhibit behavior on 'STOP' trials during which rats had to inhibit an already initiated response. Activity in mPFC was modulated by response direction and was positively correlated with accuracy and movement time in control but not PNE rats. Although the number of single neurons correlated with response direction was significantly reduced by PNE, neural activity observed on general STOP trials was largely unaffected. However, dramatic behavioral deficits on STOP trials immediately following non-conflicting (GO) trials in the PNE group appear to be mediated by the loss of conflict monitoring signals in mPFC. We conclude that prenatal nicotine exposure makes rats impulsive and disrupts firing of mPFC neurons that carry signals related to response direction and conflict monitoring.

    View details for DOI 10.1038/npp.2015.197

    View details for PubMedID 26189451

    View details for PubMedCentralID PMC4707818