Year of Publication

2007

Document Type

Dissertation

College

Medicine

Department

Anatomy and Neurobiology

First Advisor

Greg A. Gerhardt

Abstract

L-glutamate (Glu) is the predominant excitatory neurotransmitter inthe mammalian central nervous system (CNS) and is associated with a widevariety of functions including motor behavior and sensory perception. Whilemicrodialysis methods have been used to record tonic levels of Glu, little isknown about the more rapid changes in Glu signals that may occur in awakeanimals. We have previously reported acute recording methods using anenzyme-based microelectrode array (MEA) with fast temporal resolution (800msec), that is minimally invasive and is capable of detecting low levels of Glu (andlt;0.2 ??M) in anesthetized animals with little interference from other analytes. Wehave made a series of modifications to the MEA design to allow for reliablemeasures in the brain of awake behaving rats. In these studies, wecharacterized the effects of chronic implantation of the MEA into the striatum andprefrontal cortex (PFC) of Fischer 344 and Long Evans rats. We measuredresting levels of Glu and local application of Glu for 7 days without a significantloss of sensitivity and determined that Glu measures due to exogenous Gluvaried between rat strain and brain region. In addition, we determined theviability of the recordings in the brains of awake animals. We performed studiesof tail-pinch induced stress which caused an increase in Glu in the striatum andPFC of Long Evans and Fischer 344 rats. Histological data show that chronicimplantation of our MEAs caused minimal injury to the CNS. Taken together, ourdata support that chronic recordings of tonic and phasic Glu can be carried out inawake rats reliably for 7 days in vivo allowing for longer term studies of Gluregulation in behaving rats.

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