Near the base of the brain lies a group of cells (neurons), small in number but weighty in influence, that create the chemical dopamine and release it in distinct brain regions. These dopamine pathways are necessary for both the initiation of movement and the positive perception of rewards (like getting a bowl of ice cream). When this system breaks down, it can produce movement disorders like Parkinson’s disease, as well as pathological alterations in mood such as depression. Turned around, too much dopamine can conversely lead to a slew of neuropsychiatric disorders including addiction, schizophrenia, and attention deficit hyperactivity disorder (ADHD). The reason many of these disorders have poor treatment options is because we lack a basic understanding of how communication between dopamine neurons and other cells in the brain goes awry when these diseases strike. Furthermore, aging is the single most important risk factor for Parkinson’s disease, and we also lack information on how the function of single neurons can decline with age.
In the Beckstead lab, we study the communication between dopamine neurons and other cell types in the context of motivated behavior and dopamine-related diseases. Only after gaining a detailed understanding of how neuron-to-neuron communication occurs, under both normal and pathological conditions, will we be able to target these processes to better treat neurological and neuropsychiatric disorders. Further, a better understanding of how single neurons in the brain age will also inform treatment options in the very earliest stages of Parkinson’s and Alzheimer's disease, before symptoms become debilitating.
Dopamine-producing neurons in the ventral part of the midbrain are necessary for both reward learning and the initiation of voluntary movement. Their dysfunction is linked to several debilitating diseases observed throughout life, including Parkinson’s disease, addiction, and schizophrenia. In the clinic these disorders tend to have poor treatment options, in part because we lack a basic understanding of how the relevant neurocircuitry is modulated in disease states. In the Beckstead lab we explore the function of dopamine neurons at the cellular, circuit, and systems level with an eye toward preserving normal dopamine function.
Parkinson’s disease (PD) is the second most diagnosed neurodegenerative disorder, and loss of dopamine neurons of the substantia nigra is responsible for the motor impairments of the disease. Current PD treatments do not alter disease progression but instead focus on the relief of symptoms, and in order to develop strategies for halting disease progression we must first understand the adaptations that take place during the prodromal period of the disease. By using recently developed progressive mouse models of PD we are identifying the alterations in dopamine signaling that occur before the appearance of debilitating symptoms.
A second project in the lab is elucidating the relationship between dopamine neuron physiology and drug-related behavior. Abuse of drugs such as cocaine and methamphetamine is a huge public health issue, but despite decades of research there are frustratingly no FDA-approved medications to treat psychostimulant addiction. While these drugs are known to increase extracellular dopamine levels, large gaps remain in our knowledge of chronic circuit adaptations that contribute to increased drug use and addiction. Our lab uses a combination of electrophysiology, optogenetics, and behavior to explore the complex relationship between dopamine neuron excitability and drug use.
Finally, we are also investigating the effects of normal aging on single dopamine neurons. Bradykinesia is a hallmark of old age, but little is currently known about how aging affects the specific ion channels and circuits that are responsible for dopamine neuron function. We have developed reliable methodology for making electrophysiological recordings in brain slices from mice of advanced age, and are comprehensively investigating the effects of aging on the physiology of dopamine neurons.
B.S., Pharmacy, Ohio Northern University, Ada, OH, 1997
Ph.D., Pharmacology, Wake Forest University, Winston-Salem, NC, 2002
Postdoctoral Fellow, Neurophysiology, Vollum Institute, Portland, OR, 2007
Research Faculty, Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, 2008
Honors and Awards
Phi Eta Sigma freshman honorary, 1993
Office and Professional Employees Int’l Union Howard Coughlin Memorial Scholarship, 1993-1997
Mortar Board inductee, 1995
Leasure K. Darbaker award for excellence in research at Ohio Northern University, 1995, 1996
Dean’s Fellowship, Wake Forest University School of Medicine, 1997-1998
Research Society on Alcoholism meeting travel award, 2000
Individual predoctoral NRSA, F31 AA05605, 2001-2002
Individual postdoctoral NRSA, F32 DA016467, 2003
Tartar Trust Fellowship, 2004
Oregon Health & Science University Postdoctoral Paper of the Year, 2005
Society for Neuroscience NIDA Mini-symposium Early Investigator Travel Award, 2010
University of Texas Health Science Center San Antonio Distinguished Junior Research Scholar Presidential Award, 2014
J. Donald & Patricia H. Capra Award for Scientific Achievement, Oklahoma Medical Research Foundation, 2021
Institute of Integration for Medicine & Science pilot project ad hoc reviewer, 2013-2016
Fonds Wetenschappelijk Onderzoek (Flanders, Belgium) ad hoc reviewer, 2014-2015
NIH Special Emphasis Panel 05 ZRG1 MDCN-R (04) S ad hoc reviewer, 2015
NIH Special Emphasis Panel 2017/01 ZRG1 MDCN-N (02) ad hoc reviewer, 2016
NIH Special Emphasis Panel 2016/10 ZRG1 MDCN-R (04) M ad hoc reviewer, 2016
Review Committee for grant applications, Southwest National Primate Research Center, 2016-2017
Molecular Neuropharmacology and Signaling Study Section [MNPS] ad hoc reviewer, 2016-2018
Molecular Neuropharmacology and Signaling [MNPS] Study Section permanent member, 2019-2023
American Society for Pharmacology & Experimental Therapeutics [ASPET] Program Committee, 2019-present
Society for Neuroscience
American Aging Association
American Society for Pharmacology and Experimental Therapeutics
International Basal Ganglia Society
Joined OMRF’s scientific staff in 2017
Bhaskaran S, Kumar G, Thadathil N, Piekarz KM, Mohammed S, Lopez SD, Qaisar R, Walton D, Brown JL, Murphy A, Smith N, Saunders D, Beckstead MJ, Plafker S, Lewis TL Jr, Towner R, Deepa SS, Richardson A, Axtell RC, Van Remmen H. Neuronal deletion of MnSOD in mice leads to demyelination, inflammation and progressive paralysis that mimics phenotypes associated with progressive multiple sclerosis. Redox Biol 59:102550, 2022 November, PMID: 36470129, PMCID: PMC9720104
Troyano-Rodriguez E, Blankenship HE, Handa K, Branch SY, Beckstead MJ. Preservation of dendritic D2 receptor transmission in substantia nigra dopamine neurons with age. Sci Rep 13:1025, 1970 January, PMID: 36658269, PMCID: PMC9852430
Dominguez-Lopez S, Ahn B, Sataranatarajan K, Ranjit R, Premkumar P, Van Remmen H, Beckstead MJ. Long-term methamphetamine self-administration increases mesolimbic mitochondrial oxygen consumption and decreases striatal glutathione. Neuropharmacology:109436, 1970 January, PMID: 36693561
Gomez JA, Perkins JM, Beaudoin GM, Cook NB, Quraishi SA, Szoeke EA, Thangamani K, Tschumi CW, Wanat MJ, Maroof AM, Beckstead MJ, Rosenberg PA, Paladini CA. Ventral tegmental area astrocytes orchestrate avoidance and approach behavior. Nat Commun. 2019 Mar 29;10(1):1455. PMID: 30926783, PMCID: PMC6440962
Lynch WB, Tschumi CW, Sharpe AL, Branch SY, Chen C, Ge G, Li S, Beckstead MJ. Progressively disrupted somatodendritic morphology in dopamine neurons in a mouse Parkinson's model. Mov Disord. 2018 Dec;33(12):1928-1937. PMID: 30440089, PMCID: PMC6492291
Branch SY, Chen C, Sharma R, Lechleiter JD, Li S and Beckstead MJ. Dopaminergic neurons exhibit an age-dependent decline in electrophysiological parameters in the MitoPark mouse model of Parkinson's disease. J Neurosci. 2016 Apr 6;36(14):4026-37. PMID: 27053209 PMCID: PMC4821912
Branch SY, Sharma R and Beckstead M. Aging decreases L-type calcium currents and pacemaker firing fidelity in substantia nigra dopamine neurons. J Neurosci. 2014 Jul 9;34(28):9310-8. PMID: 25009264 PMCID: PMC4087208
Branch SY, Goertz RB, Sharpe AL, Pierce J, Roy S, Ko D, Paladini CA, Beckstead MJ. Food restriction increases glutamate receptor-mediated burst firing of dopamine neurons. J Neurosci. 2013 Aug 21;33(34):13861-72. PMID: 23966705 PMCID: PMC3755722
Beckstead MJ, Grandy DK, Wickman K, Williams JT. Vesicular dopamine release elicits an inhibitory postsynaptic current in midbrain dopamine neurons. Neuron. 2004 Jun 24;42(6):939-46. PMID: 15207238