I am a postdoctoral fellow interested in using multiplexing molecular, electrophysiological, and microscopy techniques to
dissect the function of brain circuits in health and disease

Honors & Awards

  • Featured Artwork, Nathan S. Kline Institute for Psychiatric Research (2021)
  • NIH Ruth L. Kirschstein National Research Service Award (F32), NIAAA (2020)
  • Featured Microscopy Image, "Beautiful Brain Exhibit", Ackland Art Museum (2019)
  • Cover Art, Genes, Brain, and Behavior (2018)
  • NIH Ruth L. Kirschstein National Research Service Award (F31), NIAAA (2017)
  • Outstanding Undergraduate Thesis Award, Phi Beta Kappa (2014)
  • PIRE Fellow, National Science Foundation (2013)

Boards, Advisory Committees, Professional Organizations

  • Member, Society for Neuroscience (2014 - Present)
  • Member, Research Society on Alcoholism (2017 - Present)

Professional Education

  • PhD, The University of North Carolina at Chapel Hill, Neuroscience (2019)
  • BS, The Pennsylvania State University, Biology (2014)

Stanford Advisors

  • Jun Ding, Postdoctoral Faculty Sponsor

All Publications

  • Motor Impairments and Dopaminergic Defects Caused by Loss of Leucine-Rich Repeat Kinase 2 Function in Mice. The Journal of neuroscience : the official journal of the Society for Neuroscience Huang, G., Bloodgood, D. W., Kang, J., Shahapal, A., Chen, P., Kaganovsky, K., Kim, J., Ding, J., Shen, J. 2022


    Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD), but the pathogenic mechanism underlying LRRK2 mutations remains unresolved. In this study, we investigate the consequence of inactivation of LRRK2 and its functional homolog LRRK1 in male and female mice up to 25months of age using behavioral, neurochemical, neuropathological, and ultrastructural analyses. We report that LRRK1 and LRRK2 double knock-out (LRRK DKO) mice exhibit impaired motor coordination at 12months of age before the onset of DA neuron loss in the substantia nigra (SNpc). Moreover, LRRK DKO mice develop age-dependent, progressive loss of DA terminals in the striatum. Evoked dopamine release measured by fast-scan cyclic voltammetry in the dorsal striatum is also reduced in the absence of LRRK. Furthermore, LRRK DKO mice at 20-25months of age show substantial loss of DA neurons in the SNpc. The surviving SNpc neurons in LRRK DKO mice at 25months of age accumulate large numbers of autophagic and autolysosomal vacuoles and are accompanied with microgliosis. Surprisingly, the cerebral cortex is unaffected, as shown by normal cortical volume and neuron number as well as unchanged number of apoptotic cells and microglia in LRRK DKO mice at 25months. These findings show that loss of LRRK function causes impairments in motor coordination, degeneration of DA terminals, reduction of evoked DA release, and selective loss of DA neurons in the SNpc, indicating that LRRK DKO mice are unique models for better understanding DA neurodegeneration in PD.SIGNIFICANCE STATEMENTOur current study employs a genetic approach to uncover the normal function of the LRRK family in the brain during mouse life span. Our multidisciplinary analysis demonstrates a critical normal physiological role of LRRK in maintaining the integrity and function of dopaminergic terminals and neurons in the aging brain, and show that LRRK DKO mice recapitulate several key features of PD and provide unique mouse models for elucidating molecular mechanisms underlying dopaminergic neurodegeneration in PD.

    View details for DOI 10.1523/JNEUROSCI.0140-22.2022

    View details for PubMedID 35534227

  • Kappa opioid receptor and dynorphin signaling in the central amygdala regulates alcohol intake. Molecular psychiatry Bloodgood, D. W., Hardaway, J. A., Stanhope, C. M., Pati, D., Pina, M. M., Neira, S., Desai, S., Boyt, K. M., Palmiter, R. D., Kash, T. L. 2020


    Excessive alcohol drinking has been shown to modify brain circuitry to predispose individuals for future alcohol abuse. Previous studies have implicated the central nucleus of the amygdala (CeA) as an important site for mediating the somatic symptoms of withdrawal and for regulating alcohol intake. In addition, recent work has established a role for both the Kappa Opioid Receptor (KOR) and its endogenous ligand dynorphin in mediating these processes. However, it is unclear whether these effects are due to dynorphin or KOR arising from within the CeA itself or other input brain regions. To directly examine the role of preprodynorphin (PDYN) and KOR expression in CeA neurons, we performed region-specific conditional knockout of these genes and assessed the effects on the Drinking in the Dark (DID) and Intermittent Access (IA) paradigms. Conditional gene knockout resulted in sex-specific responses wherein PDYN knockout decreased alcohol drinking in both male and female mice, whereas KOR knockout decreased drinking in males only. We also found that neither PDYN nor KOR knockout protected against anxiety caused by alcohol drinking. Lastly, a history of alcohol drinking did not alter synaptic transmission in PDYN neurons in the CeA of either sex, but excitability of PDYN neurons was increased in male mice only. Taken together, our findings indicate that PDYN and KOR signaling in the CeA plays an important role in regulating excessive alcohol consumption and highlight the need for future studies to examine how this is mediated through downstream effector regions.

    View details for DOI 10.1038/s41380-020-0690-z

    View details for PubMedID 32099099

    View details for PubMedCentralID PMC8124770

  • Central Amygdala Prepronociceptin-Expressing Neurons Mediate Palatable Food Consumption and Reward NEURON Hardaway, J., Halladay, L. R., Mazzone, C. M., Pati, D., Bloodgood, D. W., Kim, M., Jensen, J., DiBerto, J. F., Boyt, K. M., Shiddapur, A., Erfani, A., Hon, O. J., Neira, S., Stanhope, C. M., Sugam, J. A., Saddoris, M. P., Tipton, G., McElligott, Z., Jhou, T. C., Stuber, G. D., Bruchas, M. R., Bulik, C. M., Holmes, A., Kash, T. L. 2019; 102 (5): 1037-+


    Food palatability is one of many factors that drives food consumption, and the hedonic drive to feed is a key contributor to obesity and binge eating. In this study, we identified a population of prepronociceptin-expressing cells in the central amygdala (PnocCeA) that are activated by palatable food consumption. Ablation or chemogenetic inhibition of these cells reduces palatable food consumption. Additionally, ablation of PnocCeA cells reduces high-fat-diet-driven increases in bodyweight and adiposity. PnocCeA neurons project to the ventral bed nucleus of the stria terminalis (vBNST), parabrachial nucleus (PBN), and nucleus of the solitary tract (NTS), and activation of cell bodies in the central amygdala (CeA) or axons in the vBNST, PBN, and NTS produces reward behavior but did not promote feeding of palatable food. These data suggest that the PnocCeA network is necessary for promoting the reinforcing and rewarding properties of palatable food, but activation of this network itself is not sufficient to promote feeding.

    View details for DOI 10.1016/j.neuron.2019.03.037

    View details for Web of Science ID 000470104900015

    View details for PubMedID 31029403

    View details for PubMedCentralID PMC6750705

  • Dynorphin-kappa opioid receptor activity in the central amygdala modulates binge-like alcohol drinking in mice NEUROPSYCHOPHARMACOLOGY Anderson, R. I., Lopez, M. F., Griffin, W. C., Haun, H. L., Bloodgood, D. W., Pati, D., Boyt, K. M., Kash, T. L., Becker, H. C. 2019; 44 (6): 1084-1092


    Although previous research has demonstrated a role for kappa opioid receptor-mediated signaling in escalated alcohol consumption associated with dependence and stress exposure, involvement of the dynorphin/kappa opioid receptor (DYN/KOR) system in binge-like drinking has not been fully explored. Here we used pharmacological and chemogenetic approaches to examine the influence of DYN/KOR signaling on alcohol consumption in the drinking-in-the-dark (DID) model of binge-like drinking. Systemic administration of the KOR agonist U50,488 increased binge-like drinking (Experiment 1) while, conversely, systemic administration of the KOR antagonist nor-BNI reduced drinking in the DID model (Experiment 2). These effects of systemic KOR manipulation were selective for alcohol as neither drug influenced consumption of sucrose in the DID paradigm (Experiment 3). In Experiment 4, administration of the long-acting KOR antagonist nor-BNI into the central nucleus of the amygdala (CeA) decreased alcohol intake. Next, targeted "silencing" of DYN+ neurons in the CeA was accomplished using a chemogenetic strategy. Cre-dependent viral expression in DYN+ neurons was confirmed in CeA of Pdyn-IRES-Cre mice and functionality of an inhibitory (hM4Di) DREADD was validated (Experiment 5). Activating the inhibitory DREADD by CNO injection reduced binge-like alcohol drinking, but CNO injection did not alter alcohol intake in mice that were treated with control virus (Experiment 6). Collectively, these results demonstrate that DYN/KOR signaling in the CeA contributes to excessive alcohol consumption in a binge-drinking model.

    View details for DOI 10.1038/s41386-018-0294-3

    View details for Web of Science ID 000464017300011

    View details for PubMedID 30555162

    View details for PubMedCentralID PMC6461883

  • Fear extinction requires infralimbic cortex projections to the basolateral amygdala. Translational psychiatry Bloodgood, D. W., Sugam, J. A., Holmes, A., Kash, T. L. 2018; 8 (1): 60


    Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role. To address this outstanding issue, the current study employed a combination of electrophysiological and chemogenetic approaches in mice to interrogate the role of IL-BLA and IL-NAc pathways in extinction. Specifically, we used patch-clamp electrophysiology coupled with retrograde tracing to examine changes in neuronal activity of the IL and prelimbic cortex (PL) projections to both the BLA and NAc following fear extinction. We found that extinction produced a significant increase in the intrinsic excitability of IL-BLA projection neurons, while extinction appeared to reverse fear-induced changes in IL-NAc projection neurons. To establish a causal counterpart to these observations, we then used a pathway-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADD) strategy to selectively inhibit PFC-BLA projection neurons during extinction acquisition. Using this approach, we found that DREADD-mediated inhibition of PFC-BLA neurons during extinction acquisition impaired subsequent extinction retrieval. Taken together, our findings provide further evidence for a critical contribution of the IL-BLA neural circuit to fear extinction.

    View details for DOI 10.1038/s41398-018-0106-x

    View details for PubMedID 29507292

    View details for PubMedCentralID PMC5838104

  • Dynorphin Controls the Gain of an Amygdalar Anxiety Circuit CELL REPORTS Crowley, N. A., Bloodgood, D. W., Hardaway, J., Kendra, A. M., McCall, J. G., Al-Hasani, R., McCall, N. M., Yu, W., Schools, Z. L., Krashes, M. J., Lowell, B. B., Whistler, J. L., Bruchas, M. R., Kash, T. L. 2016; 14 (12): 2774-2783


    Kappa opioid receptors (KORs) are involved in a variety of aversive behavioral states, including anxiety. To date, a circuit-based mechanism for KOR-driven anxiety has not been described. Here, we show that activation of KORs inhibits glutamate release from basolateral amygdala (BLA) inputs to the bed nucleus of the stria terminalis (BNST) and occludes the anxiolytic phenotype seen with optogenetic activation of BLA-BNST projections. In addition, deletion of KORs from amygdala neurons results in an anxiolytic phenotype. Furthermore, we identify a frequency-dependent, optically evoked local dynorphin-induced heterosynaptic plasticity of glutamate inputs in the BNST. We also find that there is cell type specificity to the KOR modulation of the BLA-BNST input with greater KOR-mediated inhibition of BLA dynorphin-expressing neurons. Collectively, these results provide support for a model in which local dynorphin release can inhibit an anxiolytic pathway, providing a discrete therapeutic target for the treatment of anxiety disorders.

    View details for DOI 10.1016/j.celrep.2016.02.069

    View details for Web of Science ID 000372869300002

    View details for PubMedID 26997280

    View details for PubMedCentralID PMC4814306