Visit moehlelab.org for the latest information on my lab!
The overarching goal of the Moehle Laboratory is to understand the cellular, molecular, and circuitry changes that underlie both the motor and non-motor symptoms of movement disorders, and to leverage these discoveries into novel therapeutic strategies for these diseases. To this end, we have recently found that the M4 muscarinic acetylcholine receptor can directly oppose D1 dopamine receptor signaling/D1-SPN activity in the basal ganglia. Surprisingly, several lines of evidence shows this happens at the level of the substantia nigra pars reticulata and not the striatum. These novel findings have shown that hindbrain cholinergic sources of acetylcholine are as capable as striatal cholinergic interneurons in regulating basal ganglia output, and suggest that non-striatal basal ganglia structures can be directly modulated to alter the motor and non-motor symptoms of basal ganglia driven movement disorders. Importantly, these data also suggest that antagonism of the M4 receptor may be an efficacious treatment for movement disorders. The initial studies in my newly established independent laboratory will expand upon these ideas. Utilizing genetically, pharmacologically, and biochemically defined models of movement disorders (such as dystonia, Parkinson’s Disease, and Lewy Body Dementia) we will perform cutting edge pharmacological, electrophysiological, behavioral, biochemical, and in vivo fiber photometry techniques to interrogate the cellular, molecular, and circuitry level changes in the central nervous system in these model systems. These studies have the possibility to make substantial advances in our understanding of brain wide changes in diseases such as Parkinson’s Disease and dystonia, as well as provide the pre-clinical rationale to direct larger drug discovery efforts for unique targets in movement disorders.
- Lewy Body Dementia
- Movement Disorders
- Muscarinic Acetylcholine Receptors
- Parkinson’s disease