Funded Projects

Degeneration of central dopamine (DA) neurons is the key pathological feature of the brain aging diseases (Alzheimer's and Parkinson's Disease - PD/AD) and its symptoms including motor and cognitive deficits. Currently, there are no neuroprotective treatments for the diseases, however, understanding differential vulnerability among heterogeneous DA neurons may lead to neuromodulation treatments. Here, the hypothalamic A11 DA neurons are hypothesized to have a role in modulating movement via encoding sensory stimulus intensities, serving as a “sensory” DA system. However, the exact link between the A11 DA system and sensory stimuli/movement remains unclear due to limitations of in vivo methods to selectively determine and manipulate rapid DA signaling. Our central hypothesis is that (1) dysfunction of the A11 DA system is a critical contributor to motor/cognitive deficits and (2) manipulation of altered DA systems with patterned sensory stimulation/movement in a virtual reality (VR) setting may ameliorate the deficits. Our objective of this proposal is to develop the experimental setup and collect preliminary data to support our hypothesis. Aim 1. Establish a VR-based movement analysis setup for clinical and preclinical studies to understand the effects of sensory stimulation/movement on physical and cognitive functions. Aim 2. Determine how the A11 DA system encodes sensory stimuli and motor outputs using rat models of PD/AD via integration of novel DA sensing, VR-based movement analysis and neuromodulation. Our expertise in various fields (Dr. Park - DA sensing and manipulation with animal models; Dr. Tomita – Aging related cognitive deficits, Dr. Andrzejewski - a Movement Disorders Neurologist; Drs. Kang and Dutta - VR based neuromodulation and motion analysis) will allow a bench-to-bedside approach, transitioning from preclinical to clinical applications.