Michael J. Beckstead, Ph.D.
Dopamine neurons of the ventral midbrain contribute to voluntary movement, the processing of natural rewards, and the etiology of several neurological disorders including Parkinson's disease, schizophrenia and drug addiction. We use a combination of patch clamp electrophysiology and behavioral techniques to investigate hypotheses concerning the role of dopamine neuron excitability in behavior.
The role of dopamine neurotransmission in methamphetamine abuse
The abuse of psychomotor stimulants (such as methamphetamine and cocaine) is an enormous public health issue, and yet no therapeutic agent is currently approved for its treatment. Repeated exposure to these drugs produces persistent neurophysiological adaptations or “plasticity” at individual synapses in the brain. However, many of these adaptations have yet to be identified, and it is not well understood how plasticity leads to increased drug seeking and intake. We use operant self-administration of methamphetamine in mice to model human drug use, and combine this with electrophysiological studies in dopamine neurons to investigate the synaptic regulation of drug-related behaviors. Determining the neurophysiological adaptations that occur with prolonged drug use is an important first step in identifying intervention strategies to treat human drug abuse.
Effects of aging on dopamine neuron excitability
Advanced age is the leading risk factor for the development of Parkinson’s disease, suggesting that adaptations occurring in dopamine neurons during normal aging may contribute to disease development. Unfortunately, very little is known about how dopamine neuron physiology changes with age. We use patch clamp electrophysiology of dopamine neurons to identify age-related adaptations in both intrinsic ion conductances and extrinsic synaptic input. We are also using a progressive mouse model of Parkinson’s disease to take physiological “snapshots” at different stages of the neurodegenerative process to identify strategies for preserving function in dopamine neurons that are still alive.
Sharpe AL, Varela E, Bettinger L and Beckstead MJ. Methamphetamine self-administration in mice decreases GIRK channel-mediated currents in midbrain dopamine neurons. In press, International Journal of Neuropsychopharmacology.
Branch SY, Sharma R and Beckstead MJ (2014) Aging decreases L-type calcium currents and pacemaker firing fidelity in substantia nigra dopamine neurons. Journal of Neuroscience. 34: 9310-9318.
Branch SY, Goertz RB, Sharpe AL, Pierce J, Roy S, Ko D, Paladini CA, and Beckstead MJ (2013) Food restriction increases glutamate receptor-mediated burst firing of dopamine neurons. Journal of Neuroscience. 33: 13861-13872.