Dr. Leventhal recently completed a clinical and research fellowship in Movement Disorders at the University of Michigan, where he also did his Neurology residency. He holds the M.D. and Ph.D. (Biomedical Engineering) degrees from Case Western Reserve University. His background in Engineering, Neuroscience, and clinical Neurology will allow him to establish a distinctive research program centered on in vivo electrophysiology in animal models of Movement Disorders, coupled with complementary recordings in human subjects. To achieve this long-term goal, a career development plan is proposed that includes continued training in in vivo electrophysiological and ontogenetic techniques, coursework, conference attendance, and limited clinical and teaching responsibilities. By the end of the award period, his goal is to have established an independent laboratory focused on in vivo animal electrophysiology, be performing complementary electrophysiological experiments in human subjects, and have clinical duties in the Movement Disorders and DBS programs. The research plan focuses on important questions regarding the systems-wide electrophysiological changes observed in Parkinson Disease (PD). Synchronized neuronal beta (~15 - 30 Hz) oscillations are tightly correlated with motor impairment, but it remains an open question whether this aberrant neural activity causes clinical symptoms. This is an important issue because therapeutic deep brain stimulation (DBS) is believed to work by disrupting pathologic beta oscillations. These experiments will address several critical gaps in the literature. First, are enhanced beta oscillations linked to dopamine loss or motor impairment? Second, what is the role of the thalamus in generating beta rhythms? Finally, how are dopamine, beta rhythms, and fine motor control related? To address these questions, Dr. Leventhal will use innovative behavioral, electrophysiological, and ontogenetic techniques in awake, behaving rats. It is hypothesized that thalamic firing patterns drive beta oscillations, which cause the bradykinesia and rigidity of PD. At the end of the award period, Dr. Leventhal will be poised to establish a sustainable research program based upon the results of these studies and his ability to perform complementary electrophysiological experiments in animals and humans.

Public Health Relevance

Specific changes in neuronal firing patterns ('beta' oscillations) have been recorded in the brains of Parkinson's disease (PD) patients and parkinsonian animals, but it is not clear if these changes cause the motor impairments of PD. This is an important question because therapeutic deep brain stimulation (DBS) is believed to work by disrupting 'pathological' neuronal oscillations. I will investigate the behavioral correlats and neural mechanisms underlying beta rhythms in healthy and parkinsonian rats.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Clinical Investigator Award (CIA) (K08)
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Neurological Sciences Training Initial Review Group (NST)
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Sieber, Beth-Anne
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
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Gaidica, Matt; Hurst, Amy; Cyr, Christopher et al. (2018) Distinct Populations of Motor Thalamic Neurons Encode Action Initiation, Action Selection, and Movement Vigor. J Neurosci 38:6563-6573
Albin, Roger L; Leventhal, Daniel K (2017) The missing, the short, and the long: Levodopa responses and dopamine actions. Ann Neurol 82:4-19
Mirzaei, Amin; Kumar, Arvind; Leventhal, Daniel et al. (2017) Sensorimotor Processing in the Basal Ganglia Leads to Transient Beta Oscillations during Behavior. J Neurosci 37:11220-11232
Mallet, Nicolas; Schmidt, Robert; Leventhal, Daniel et al. (2016) Arkypallidal Cells Send a Stop Signal to Striatum. Neuron 89:308-16
Ellens, Damien J; Gaidica, Matt; Toader, Andrew et al. (2016) An automated rat single pellet reaching system with high-speed video capture. J Neurosci Methods 271:119-27
Leventhal, Daniel K; Stoetzner, Colin; Abraham, Rohit et al. (2014) Dissociable effects of dopamine on learning and performance within sensorimotor striatum. Basal Ganglia 4:43-54
Pappas, Samuel S; Leventhal, Daniel K; Albin, Roger L et al. (2014) Mouse models of neurodevelopmental disease of the basal ganglia and associated circuits. Curr Top Dev Biol 109:97-169
Ellens, Damien J; Leventhal, Daniel K (2013) Review: electrophysiology of basal ganglia and cortex in models of Parkinson disease. J Parkinsons Dis 3:241-54