Nora McCall

Ph.D. 2019

Thesis Title:

G-protein-gated potassium channels in ventral tegmental area dopamine neurons temper behavioral sensititvity to cocaine.

Current Position:

Postdoctoral Associate, University of Pennsylvania

Undergraduate Institution and Major:

Colby College, B.A. in Biology, 2011

Graduate Advisor:

Kevin Wickman, Ph.D., Department of Pharmacology

    Description of Graduate Research:

    A long-term goal of work in the Wickman lab is to understand the mechanisms and relevance underlying drug-induced adaptations in key neuron populations implicated in addiction. We recently described a transient cocaine-induced suppression of G protein-dependent inhibitory signaling in dopamine (DA) neurons of the ventral tegmental area (VTA), a key element in the mesocorticolimbic system. This cocaine-induced adaptation required activation of D2 DA receptors and involved the internalization of G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels, a key contributor to inhibitory feedback pathways that normally temper DA neurotransmission in the mesocorticolimbic system. The goals of my project are to better understand the mechanisms and neurophysiological impact underlying the cocaine-induced suppression of GIRK-dependent signaling in VTA DA neurons and to determine the impact of GIRK channel manipulation in DA neurons on cocaine-induced reward-related behavior. To address these questions, I use brain slice electrophysiology and behavioral analysis, in tandem with pharmacologic and neuron-specific genetic manipulations of GIRK-dependent signaling in mice. My research will expand our understanding of inhibitory cell signaling mechanisms that underlie drug addiction and will provide an initial assessment of the potential utility of GIRK channel manipulation for the treatment or prevention of addiction.

    Graduate Publications:

    • DeBaker MC, Marron Fernandez de Velasco E, McCall NM, Lee AM, Wickman K. Differential impact of inhibitory G protein signaling pathways in ventral tegmental area dopamine neurons on behavioral sensitivity to cocaine and morphine. eNeuro. 2021 Mar 10:ENEURO.0081-21.2021.
    • McCall NM, Fernandez de Velasco EM, Wickman K. GIRK channel activity in dopamine neurons of the ventral tegmental area bi-directionally regulates behavioral sensitivity to cocaine. J Neurosci. 2019;39(19):3600-3610.
    • McCall NM, Kotecki L, Dominguez-Lopez S, de Velasco EM, Carlblom N, Sharpe AL, Beckstead MJ, Wickman K. Selective ablation of GIRK channels in dopamine neurons alters behavioral effects of cocaine in mice. Neuropsychopharmacology. 2017;42(3):707-715.
    • Kotecki L, Hearing M, McCall NM, Marron Fernandez de Velasco E, Pravetoni M, Arora D, Victoria NC, Munoz MB, Xia Z, Slesinger PA, Weaver CD, Wickman K. GIRK channels modulate opioid-induced motor activity in a cell type- and subunit-dependent manner. J Neurosci. 2015;35(18):7131-7142.
    • Marron Fernandez de Velasco E, McCall NM, Wickman K. GIRK channel plasticity and implications for drug addiction. Int Rev Neurobiol. 2015;123:201-238.

    Graduate Oral Presentations:

    • McCall N*, Wickman K. Inhibitory G protein signaling in dopamine neurons: a dimmer for addiction? Invited talk given at the 11th Annual Biomedical Sciences Graduate Programs Research Recognition Day, Minneapolis, MN, May 2018
    • McCall N*, Wickman K. Inhibitory G protein signaling in VTA DA neurons: a barrier to addiction? Invited talk given at the 3rd Annual Wallin Neuroscience Discovery Day, Minneapolis, MN, May 2018.
    • McCall N*, Wickman K. Selective manipulation of inhibitory signaling in dopamine neurons of the ventral tegmental area alters drug-related behavior. Talk given at University of Minnesota Graduate Program in Neuroscience Colloquium, Minneapolis, MN, February 2018
    • McCall N*, Wickman K. GIRK channels in VTA DA neurons: a barrier to addiction? Invited talk given at the 50th Winter Conference on Brain Research in Big Sky, MT, January 2017, in session “Ion Channels, Receptors and Cell Structure that Define Dopamine Neurons” chaired by John Williams. Talk also given at University of Minnesota Graduate Program in Neuroscience Colloquium, Minneapolis, MN, February 2017
    • McCall N*, Wickman K. Inhibitory G protein signaling in dopamine neurons regulates behavioral sensitivity to cocaine. Talk given at University of Minnesota Graduate Program in Neuroscience Colloquium, Minneapolis, MN, March 2016

    Graduate Abstracts:

    • McCall NM*, Marron Fernandez De Velasco E, Wickman K. Selective manipulation of inhibitory signaling in dopamine neurons of the ventral tegmental area alters behavioral response to cocaine. Poster presented at the Society for Neuroscience Annual Meeting, San Diego, CA, November 2018
    • McCall NM*, Marron Fernandez De Velasco E, Wickman K. Selective manipulation of inhibitory signaling in dopamine neurons of the ventral tegmental area alters drug-related behavior. Poster presented at the Special Poster Session at Winter Conference for Brain Research, Whistler, BC, CA, January 2018; and Graduate Program in Neuroscience Annual Retreat, Minneapolis, MN, February 2018; 11th Annual Biomedical Sciences Graduate Programs Research Recognition Day, Minneapolis, MN, May 2018
    • McCall NM*, Marron Fernandez De Velasco E, Wickman K. Selective manipulation of inhibitory signaling in dopamine neurons of the ventral tegmental area bi-directionally alters anxiety- and cocaine-related behavior. Poster presented at the Pharmacology Department Annual Retreat, Minneapolis, MN September 2017
    • McCall NM*, Kotecki L, Dominguez-Lopez S, Marron Fernandez De Velasco E, Carlblom N, Sharpe AL, Beckstead MJ, Wickman K. Selective ablation of GIRK channels in dopamine neurons alters behavioral effects of cocaine in mice. Poster presented at the Society for Neuroscience Annual Meeting, San Diego, CA, November 2016; Graduate Program in Neuroscience Annual Retreat, Minneapolis, MN February 2017; Biomedical Research Recognition Day, University of Minnesota, Minneapolis, MN, May 2017
    • McCall N, Kotecki L, Victoria N, Carlbolm N, Wickman K. GIRK channels in VTA DA neurons regulate sensitivity to cocaine-related behaviors. Abstract for poster presentation, Winter Conference on Brain Research, Breckenridge, CO; Graduate Program in Neuroscience Annual Retreat 2016, University of Minnesota, Minneapolis, MN, 2016.
    • McCall NM, Victoria N, Kotecki L, Wickman K. Stress-induced GIRK channel signaling in midbrain neurons: implications for addiction. Abstract for poster presentation, Graduate Program in Neuroscience Annual Retreat 2015, University of Minnesota, Minneapolis, MN, 2015.

    Graduate Awards:

    • 2018 Trainee Professional Development Award, Society for Neuroscience
    • 2018 Beatrice Z. Milne and Theodore Brandenburg Award, Medical School, University of Minnesota
    • 2018 University of Minnesota Council of Graduate Students Travel Award, for travel to the 2018 Winter Conference on Brain Research
    • 2018 Stark Award for Advanced Scholarship, Graduate Program in Neuroscience, University of Minnesota, for travel to the 2018 Winter Conference on Brain Research
    • 2017 First Prize Graduate Student Poster, Louise M. Nutter Poster Session Award, Department of Pharmacology Retreat, University of Minnesota
    • 2017 Travel Fellow, Winter Conference on Brain Research
    • 2016 University of Minnesota Council of Graduate Students Travel Award, for travel to the 2016 Society for Neuroscience Meeting
    • 2016-present Louise Ruth L. Kirschstein National Research Service Award (F31 NRSA), NIDA
    • 2016 Sping and Ying Ngoh Lin Award

    GPN Committees:

    • Seminar Committee, 2014-2016

    Professional Outreach:

    • Sp, Su, Fa 2018, Travel Grant Reviewer, Council of Graduate Students, University of Minnesota
    • 2017 Outreach Participant, Winter Conference on Brain Research
    • 2014-2015 Science Fair Judge, Murray Middle School, St. Paul, Minnesota
    • 2014-2017 Brain Awareness Week Presenter, University of Minnesota
    • 2014 – 2018 Minnesota State Fair Presenter, Graduate Program in Neuroscience, University of Minnesota

    Professional Memberships:

    • Society for Neuroscience, 2013-present

    Thesis Committee Members:

    Rotations:

    Research Areas:

    • Drug Abuse and Addiction

    Why Did You Choose UMN?

    I chose UMN because several faculty studied topics in which I was interested – drug addiction and stress/anxiety – and also had funding from the NIH. I have really enjoyed being a part of the community of researchers studying drug abuse and addiction brought together by the institutional NIDA training grant.

    What Advice Would You Give A First Year Graduate Student?

    Ask questions!!! Ask questions if you don’t know something, ask questions if you are curious about something. Look for answers by talking with your PI and your peers, and by searching the literature!

    McCall