Effects of NMDA Receptor Antagonist to Induce Cortical Activation in Vivo
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Authors
Vu, Anh-Tu
Issue Date
2016
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
N-methyl-D-aspartate (NMDA) is an amino acid derivative that mimics the action of glutamate at the NMDA receptor (NMDAR). Many NMDAR experiments have been studied in vitro. While clinical knowledge can be derived from in vitro experiments, in vivo studies are crucial to successfully test hypothesis put forward from these in vitro findings. In this study, an NMDAR antagonist was used to alter the thalamocortical system, which is responsible for various oscillatory rhythms. The disruption of thalamocortical oscillations and the induction of cortical activation was achieved using ketamine, a non-competitive and non-selective NMDAR antagonist. In order to analyze cortical activities from ketamine, screw electrodes were placed using stereotactic procedures to measure local field potential (LFP). Additionally, intracerebroventricular (ICV) cannulas were placed as a method of ketamine delivery. These screw electrodes allowed for biological recording which were screened for delta (0.1-4 Hz) and theta frequency (6-10 Hz) oscillations using spectral analysis. Subcutaneous ketamine was found to alter brain activity in the gamma (40-100 Hz) and high frequency band (120-180Hz) and induced locomotion in mild doses. On the other hand, ICV ketamine failed to alter cortical activities from baseline while ICV ANGII, a dipsogen, successfully induced thirst through the subfornical organ of the brain. The success of subcutaneous ketamine, ICV ANGII and failure of ICV ketamine warrant further analysis of ketamine’s property when given via ICV. Through further analysis of ketamine’s property and other NMDAR antagonist’s property, we can provide a stronger foundation for understanding cortical activities when testing a more selective NMDAR antagonist.
Description
v, 35 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.