Friday, November 16, 2018

Neurology/Neuroscience Research Seminar presented by Dr. Stella M. Papa, Associate Professor, Emory University School of Medicine - Friday, November 16th at Noon in 5515 BSRB

12:00 PM to 1:00 PM

Biomedical Science Research Bldg, Rm 5515, 109 Zina Pitcher Pl., Ann Arbor, MI 48109

The key role of striatal dysfunction in Parkinson’s disease

Neurodegeneration of nigrostriatal cells in Parkinson’s disease (PD) deprives the striatum of dopamine modulation thereby altering the excitability of striatal output neurons. These striatal changes largely influence the cortico-basal ganglia circuitry. In addition, extrastriatal dopamine mechanisms and adaptive changes of other signaling systems in this network also contribute to dysfunction.  Nevertheless, the use of modern optogenetic and chemogenetic technologies to selectively manipulate cellular populations particularly in rodent models has recently demonstrated a critical role of the striatal projection neurons (SPNs). The abnormal signaling from indirect pathway SPNs was proven to drive plasticity changes in cortico-subthalamic synapses. Recent studies also indicate that a subset of direct pathway SPNs may be responsible for the expression of abnormal movement in response to dopaminergic stimulation. Furthermore, primate models that parallel the phenotype of advanced disease have evidenced major dysregulation of SPNs. Critically, striatal recordings in humans have shown similar alterations of the SPN activity in PD. These profound changes are likely the product of multiple interacting signals that participate in the complex SPN microcircuitry, but the glutamate transmission is the top candidate to play a central role. Indeed, the stability of SPN responses to dopamine modulation is under the control of NMDAR and AMPAR transmission in parkinsonian primates. We have just begun to profile the striatal dysfunction, but next studies analyzing molecular pathways with high cell resolution in refined models may help dissect the specific mechanisms of motor abnormalities in PD.