Li Cai

Defense Date

10-31-2008

Graduation Date

Fall 2008

Availability

Immediate Access

Submission Type

thesis

Degree Name

MS

Department

Pharmacology-Toxicology

Committee Chair

David A. Johnson

Committee Member

Christopher K. Surratt

Committee Member

Jane Cavanaugh

Committee Member

James K. Drennen

Keywords

Cholinergic deficit, Medial septum, hippocampus, septal-hippocampal tract, 192IgG-saporin, object recognition memory, spatial recognition memory, amnesia, Alzheimer's disease

Abstract

The objective of this study was to clarify the role of septal-hippocampal cholinergic neurons in object and spatial recognition memory. Stereotaxic-surgical infusion of the selective cholinergic neurotoxin, 192IgG-saporin (SAP), into the medial septum (MS) of Sprague-Dawley rats was utilized to establish an animal model of cholinergic deficit of the septal-hippocampal tract, which had been expected as a pathologic model of memory impairment for Alzheimer's disease (AD). Three types of recognition memory were examined: retrograde object recognition, anterograde object recognition, and anterograde spatial recognition. These were examined with a modified version of a standard object recognition paradigm. For retrograde memory retention testing, rats received SAP after training; in contrast, for anterograde retention testing, rats received SAP before training. The time that the rats spent exploring familiar and novel objects or familiar objects in a novel location was measured. The effects of SAP on the three types of recognition memory were tested and compared to control animals. There was no significant difference in the mean exploration ratios (MERs) between control rats infused with artificial cerebrospinal fluid (aCSF) and control rats that did not receive surgery (NOR). The MERs for both control groups were in the range between 0.6-0.7, consistent with the object recognition testing literature. These results indicate that the infusion surgery itself had no effect on object or spatial recognition memory and that the methodology for object and spatial recognition developed for this study worked well. SAP lesioned rats did not demonstrate impairment of retrograde object recognition memory (0.68±0.04 vs 0.67±0.03, p = 0.888) and also displayed normal anterograde object recognition memory (0.67±0.04 vs 0.66±0.02, p = 0.866) compared to control rats. However, compared to controls, SAP rats were significantly impaired in anterograde spatial recognition memory as reflected in the fall of the MER for the SAP group to chance levels (0.51±0.04 vs 0.62±0.02. p = 0.0081). These findings suggest that the septal-hippocampal cholinergic neurons play an important role for spatial recognition memory, but not for object recognition memory and indicate that the septal-hippocampal cholinergic deficit may be responsible for the mild memory impairments shown in the early phase of AD.

Format

PDF

Language

English

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