Role of Adrenergic Neurons in Motor Control: Examination of Cerebellar Purkinje Neurons in Mice Following Selective Adrenergic Cell Ablation in Vivo

Phenylethanolamine-N-methyltransferase (Pnmt) is the enzyme that catalyzes the conversion of noradrenaline to adrenaline. These catecholamines are synthesized in the medulla of the adrenal gland and by some neurons of the central nervous system. The precise location of Pnmt action in the brain and its physiological significance are unknown. Prior studies led by Aaron Owji, a graduate student in Dr. Ebert’s laboratory, showed that mice with selectively ablated Pnmt cells show signs of neurological defects such as abnormal gait, weakened grip strength, lack of balance, reduced movement, and defective reflexes during tail suspension tests. The cerebellum is a small section of the brain that is responsible for fine-tuning motor commands. Since the Purkinje cells of the cerebellum act as the sole source of output from the cerebellar cortex, impairment of these cells could possibly account for the motor deficits seen in the mice models. The purpose of this project is to determine if there is indeed a change in Purkinje cells between wild type mice and Pnmt-ablated mice. The first aim is to identify quantitative differences in cell count between both genotypes. The second aim is to determine any morphological changes in the Purkinje cells. The main technique used in this project is immunohistochemistry in which cerebellum tissue from mice models are stained with Calbindin (a cellular marker for Purkinje neurons) and imaged with a confocal microscope. Results showed a slight reduction in the Purkinje cells of the ablated mice compared to the control genotype, accompanied with observable differences in cell structure. Understanding catecholamine pathway mechanisms in the nervous system is imperative for elucidating and targeting key players in neurodegenerative disorders