Michael Beckstead, Ph.D.

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.

Education
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
1993 Phi Eta Sigma freshman honorary
1993-97 Office and Professional Employees Int’l Union Howard Coughlin Memorial Scholarship
1995 Mortar Board inductee
1995-96 Leasure K. Darbaker award for excellence in research at Ohio Northern University (twice)
1997-98 Dean’s Fellowship, Wake Forest University School of Medicine
2000 Research Society on Alcoholism meeting travel award
2001-02 Individual predoctoral NRSA, F31 AA05605
2003 Individual postdoctoral NRSA, F32 DA016467
2004 Tartar Trust Fellowship
2005 Oregon Health & Science University Postdoctoral Paper of the Year
2010 Society for Neuroscience NIDA Mini-symposium Early Investigator Travel Award
2014 University of Texas Health Science Center San Antonio Distinguished Junior Research Scholar Presidential Award
2021 J. Donald & Patricia H. Capra Award for Scientific Achievement (OMRF)

Other Activities
Institute of Integration for Medicine & Science pilot project ad hoc reviewer (2013-16)
Fonds Wetenschappelijk Onderzoek (Flanders, Belgium) ad hoc reviewer (2014-15)
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 (2016-17)
Molecular Neuropharmacology and Signaling Study Section [MNPS] ad hoc reviewer (2016-18)
Molecular Neuropharmacology and Signaling [MNPS] Study Section permanent member (2019-23)
American Society for Pharmacology & Experimental Therapeutics [ASPET] Program Committee (2019-)

Memberships
Society for Neuroscience
American Aging Association
American Society for Pharmacology and Experimental Therapeutics
International Basal Ganglia Society

Joined OMRF’s Scientific Staff in 2017

View more publications

Recent Publications

Beckstead MJ, Howell RD. Progressive parkinsonism due to mitochondrial impairment: Lessons from the MitoPark mouse model. Exp Neurol:113707, 2021 March, PMID: 33753138, PMCID: PMC8169575

Chucair-Elliott AJ, Ocañas SR, Stanford DR, Ansere VA, Buettner KB, Porter H, Eliason NL, Reid JJ, Sharpe AL, Stout MB, Beckstead MJ, Miller BF, Richardson A, Freeman WM. Inducible cell-specific mouse models for paired epigenetic and transcriptomic studies of microglia and astroglia. Commun Biol 3:693, 2020 November, PMID: 33214681, PMCID: PMC7678837

Howell RD, Dominguez-Lopez S, Ocañas SR, Freeman WM, Beckstead MJ. Female mice are resilient to age-related decline of substantia nigra dopamine neuron firing parameters. Neurobiol Aging 95:195-204, 2020 August, PMID: 32846275, PMCID: PMC7606778

Selected Publications

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

Aging & Metabolism Research Program, MS 21
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104

Phone: (405) 271-7575
Fax: (405) 271-1437
E-mail: mike-beckstead@omrf.org

Matthew Higgs, Ph.D.
Staff Scientist

Eva Troyano Rodriguez, Ph.D.
Assistant Staff Scientist

Sergio Dominguez Lopez, Ph.D.
Postdoctoral Fellow

Casey Gilmore
Senior Research Technician

Marta Trzeciak
Senior Research Technician

Kylie Handa
Research Technician

Becca Howell
Research Assistant

News from the Beckstead lab

OMRF receives grant for Alzheimer’s research

July 27, 2021

The National Institutes of Health has awarded the Oklahoma Medical Research Foundation $480,000 for research on dopamine’s role in Alzheimer’s disease.

Understanding the differences between Alzheimer’s and dementia

June 22, 2021

For years, the terms “Alzheimer’s” and “dementia” have been used interchangeably. But the difference between them is important.

OMRF honors scientists, board member at spring meeting

April 29, 2021

OMRF awarded scientific prizes to four scientists and honored a board member on Tuesday at its spring board meeting.

OMRF scientist receives Alzheimer’s grant

July 22, 2019

Alzheimer’s affects 5.8 million Americans, and one in three senior citizens dies with the disease or other forms of dementia.

Taking action: OMRF researcher starts lab investigating vital chemical 

March 6, 2018

Dopamine is a chemical responsible for voluntary movement and the perception of rewards in the brain.

Presbyterian Health Foundation awards more than $3.7 million in grants to OUHSC, OMRF

July 17, 2017

Since 1985, PHF has awarded grants totaling more than $160 million.