UVM Theses and Dissertations
Format:
Print
Author:
Lipatova, Olga
Dept./Program:
Psychology
Year:
2014
Degree:
Ph. D.
Abstract:
The present dissertation provides a broad overview of estrogen's regulatory function in neurobiological and behavioral processes that are involved in systems of learning and memory, as well as emotion regulation. The purpose of the research presented here is toadvance the current literature regarding the role of estrogen in age related cognitive decline, as well as psychopathology related to mood disorders. To do so, we utilize a number of behavioral and molecular techniques within experimental procedures in a rodent animal model. Overall, estrogen has been shown to either enhance or impair learning and memory in female rats. The use of different experimental paradigms or estrogen treatment regimens may contribute to these disparate findings.
In order to assess the effect of different estradiol (E2) treatments on several aspects of cognition, we trained ovariectomized female rats with either continuous, cycling, or sham E2-replacement, in an open-field tower maze task (OFTM) designed to test reference memory in a low-stress enviroment. In addition, in order to compare two distinct learning and memory systems, rats were trained to use either a dorsolateral striatum-based response type learning or a hippocampal-based place type learning to solve the maze. Results showed that cyclic, but not continuous, E2-replacement facilitated the acquisition of spatial memory in place-learners.
Neither E2 regimen affected acquisition in response-learners. Additionally, when all experimental groups were performing at asymptote, rats were evaluated for performance stability by changing the location of their start position in the OFTM. Both regimens of E2 disrupted the expression of spatial memory in place-learners following the novel start position. However, E2-replacement protected OVX female rats from the disruption of memory expression following a start position change in response-learners. Additionally all experimental groups performed equally well when tested following a 21-day period during which rats were absent from the maze. These results suggest that E2 fluctuation is particularly important in the acquisition of hippocampal-mediated spatial learning, and that hippocampal-based memory may be subject to disruption following environmental change, while striatum-based memory is subject to protection.
Additionally, given the wide role of E2 in the serotonin system and the unique location and function of the specific serotonin subtype receptor: serotonin 6 receptor (5-HT₆R) we used a quantitative PCR technique to investigate modulatory effects of E2 on the expression of this receptor. The results indicated that E2 regulates mRNA expression of the 5-HT₆R in a sex-and brain region-specific manner. Given these findings we set out to investigate the functional role this part of a molecular mechanism serves. Provided the result that E2 down-regulated 5-HT₆R in the dorsolateral striatum (DLS) we utilized a task known to involve this brain region (Set 1 of a Set-Shift task).
The results demonstrated that ovariectomized female rats were impaired on acquisition of the Set 1 rule. Furthermore, we demonstrated that infusion of a 5-HT₆R agonist directly into the DLS appears to reduce the impairment in acquisition of the DLS dependent task observed in E2-replaced female rats. These results imply that down-regulation of the 5-HT₆R in the DLS may in fact be an element of a mechanism by which E2 regulates striatum-dependent behavior. The discussion of the cumulative results reported in this dissertation describe how these findings integrate with and advance current literature. In addition, we offer potential clinical implications that can be made based on this data.
In order to assess the effect of different estradiol (E2) treatments on several aspects of cognition, we trained ovariectomized female rats with either continuous, cycling, or sham E2-replacement, in an open-field tower maze task (OFTM) designed to test reference memory in a low-stress enviroment. In addition, in order to compare two distinct learning and memory systems, rats were trained to use either a dorsolateral striatum-based response type learning or a hippocampal-based place type learning to solve the maze. Results showed that cyclic, but not continuous, E2-replacement facilitated the acquisition of spatial memory in place-learners.
Neither E2 regimen affected acquisition in response-learners. Additionally, when all experimental groups were performing at asymptote, rats were evaluated for performance stability by changing the location of their start position in the OFTM. Both regimens of E2 disrupted the expression of spatial memory in place-learners following the novel start position. However, E2-replacement protected OVX female rats from the disruption of memory expression following a start position change in response-learners. Additionally all experimental groups performed equally well when tested following a 21-day period during which rats were absent from the maze. These results suggest that E2 fluctuation is particularly important in the acquisition of hippocampal-mediated spatial learning, and that hippocampal-based memory may be subject to disruption following environmental change, while striatum-based memory is subject to protection.
Additionally, given the wide role of E2 in the serotonin system and the unique location and function of the specific serotonin subtype receptor: serotonin 6 receptor (5-HT₆R) we used a quantitative PCR technique to investigate modulatory effects of E2 on the expression of this receptor. The results indicated that E2 regulates mRNA expression of the 5-HT₆R in a sex-and brain region-specific manner. Given these findings we set out to investigate the functional role this part of a molecular mechanism serves. Provided the result that E2 down-regulated 5-HT₆R in the dorsolateral striatum (DLS) we utilized a task known to involve this brain region (Set 1 of a Set-Shift task).
The results demonstrated that ovariectomized female rats were impaired on acquisition of the Set 1 rule. Furthermore, we demonstrated that infusion of a 5-HT₆R agonist directly into the DLS appears to reduce the impairment in acquisition of the DLS dependent task observed in E2-replaced female rats. These results imply that down-regulation of the 5-HT₆R in the DLS may in fact be an element of a mechanism by which E2 regulates striatum-dependent behavior. The discussion of the cumulative results reported in this dissertation describe how these findings integrate with and advance current literature. In addition, we offer potential clinical implications that can be made based on this data.