Dopamine modulation of NMDA receptor subunit GluN2A function in indirect pathway striatal projection neurons in Parkinson’s Disease Restricted; Files Only
Li, Yujia (Fall 2022)
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Dopaminergic neurons in SNc project to the striatum, the recipient area for information that reach the basal ganglia. Dopamine (DA) modulates striatal projection neurons (SPNs) of the striatum by upregulating the firing rates of SPNs expressing the dopamine 1 receptors (D1Rs) and downregulating the firing rates of SPNs expressing the dopamine 2 receptors (D2Rs). Based on the differential neuronal projections, the two SPN subtypes are known as the direct pathway SPNs (dSPNs) and the indirect pathway SPNs (iSPNs) respectively. Previous studies have found that in PD, the loss of DA modulation may lead to SPN hyperactivity and a differential change in firing patterns between dSPNs and iSPNs. Further evidence suggested that glutamatergic signaling, including NMDA receptor-mediated excitatory postsynaptic currents (EPSCs), may play a role in the altered SPN activities. This study investigated the functional change of the GluN2A subunit of the NMDA receptor (NMDAR) in iSPNs in PD, using a 6-OHDA lesioned hemiparkinsonian rat model. We did not find a significant difference in GluN2A-mediated EPSCs between iSPNs of DA-intact and DA-depleted striatum. iSPN hyperactivity and firing pattern changes in PD are likely not due to changes in Glu2A-mediated EPSC.
Table of Contents
Introduction
Materials and Methods
6-OHDA lesioned hemiparkinsonian rat model
Virus injection
Apomorphine Test
Brain Slice Preparation
Whole Cell Electrophysiology Recording
RNAscope Assay
Statistical Analysis
Results
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Discussion
Conclusion
References
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File download under embargo until 11 January 2025 | 2022-12-13 23:31:17 -0500 | File download under embargo until 11 January 2025 |
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