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Chronic stress often leads to cognitive deficits, especially within the spatial memory domain mediated by the hippocampus. When chronic stress ends and a no-stress period ensues (i.e., washout, WO), spatial ability improves, which can be better than non-stressed controls (CON). The WO period is often the same duration as the

Chronic stress often leads to cognitive deficits, especially within the spatial memory domain mediated by the hippocampus. When chronic stress ends and a no-stress period ensues (i.e., washout, WO), spatial ability improves, which can be better than non-stressed controls (CON). The WO period is often the same duration as the chronic stress paradigm. Given the potential benefit of a post-stress WO period on cognition, it is important to investigate whether this potential benefit of a post-stress WO period has long-lasting effects. In this project, chronic restraint (6hr/d/21d) in Sprague-Dawley rats was used, as it is the minimum duration necessary to observe spatial memory deficits. Two durations of post-stress WO were used following the end of chronic restraint, 3 weeks (STR-WO3) and 6 weeks (STR-WO6). Immediately after chronic stress (STR-IMM) or the WO periods, rats were tested on various cognitive tests. We corroborated past studies that chronic stress impaired spatial memory (STR-IMM vs CON). Interestingly, STR-WO3 and STR-WO6 failed to demonstrate improved spatial memory on a radial arm water maze task, performing similarly as STR-IMM. Performance outcomes were unlikely from differences in anxiety or motivation because rats from all conditions performed similarly on an open field task and on a simple object recognition paradigm, respectively. However, performance on object placement was unusual in that very few rats explored, suggesting some degree of anxiety or fear in all groups. One possible interpretation of the unusual results of the 3 week washout group may be attributed to the different spatial memory tasks used across studies or external factors from the study. Further exploration of these other factors led to the conclusion that they did not play a role and the STR-WO3 RAWM data were anomalous to other studies. This suggests that a washout period following chronic stress may not be fully understood.
ContributorsFlegenheimer, Aaron Embden (Author) / Conrad, Cheryl (Thesis director) / Bimonte-Nelson, Heather (Committee member) / Ortiz, J. Bryce (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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The capacity to track time in the seconds-to-minutes range, or interval timing, appears to be at least partially dependent on intact hippocampal (HPC) function. The current dissertation sought to dissociate timed responses, non-timed responses, and motivational aspects of behavior in order to propose a role of the HPC in specific

The capacity to track time in the seconds-to-minutes range, or interval timing, appears to be at least partially dependent on intact hippocampal (HPC) function. The current dissertation sought to dissociate timed responses, non-timed responses, and motivational aspects of behavior in order to propose a role of the HPC in specific timing sub-processes. In Chapter 2, effects of dorsal HPC (dHPC) lesions on temporal responding in a switch-timing task revealed a critical role of dHPC in the acquisition of interval timing criteria. Following dHPC lesions, the start time of responding was systemically shortened, in a manner that was enhanced and sustained when encoding a novel long interval, consistent with a memory-based account of dHPC function in timed responding. Chapter 3 investigated effects of chronic stress, which has been shown to reliably induce HPC dendritic retraction, on interval timing, utilizing response-initiated schedules of reinforcement, which facilitate deconvolution of timing and motivation. This revealed task-dependent effects on interval timing and motivation, where stress induced transient effects on motivation in a prospective timing task, but transient effects on the variability of timed responding in a retrospective timing task, consistent with an effect on memory function in interval timing. Chapter 4 sought to bring timed responding, motivation, and non-timed behaviors under stronger procedural control, through the implementation of a response-initiated timing-with-opportunity-cost task, in which a cost is imposed on temporal food-seeking by the presence of a concurrent source of probabilistic reinforcement. This arrangement garnered strong schedule control of behavior, and revealed individual-subject differences in the effects of reward devaluation, such that it affected motivation in some rats, but temporal responding in others. Using this methodology, Chapter 5 investigated initial temporal entrainment of behavior under pharmacological deactivation of dHPC and revealed its critical involvement in updating memory to new temporal contingencies. Together, data from this dissertation contrast with prior conclusions that the HPC is not involved in learning temporal criteria, and instead suggest that its function is indeed critical to encoding temporal intervals in memory.
ContributorsGupta, Tanya A. (Author) / Sanabria, Federico (Thesis advisor) / Conrad, Cheryl (Committee member) / Olive, Foster (Committee member) / McClure, Samuel (Committee member) / Arizona State University (Publisher)
Created2022
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Description
Major Depressive Disorder (MDD) affects over 300 million people worldwide, with the hippocampus showing decreased volume and activity in patients with MDD. The current study investigated whether a novel preclinical model of depression, unpredictable intermittent restraint (UIR), would decrease hippocampal neuronal dendritic complexity. Adult Sprague Dawley rats (24 male, 24

Major Depressive Disorder (MDD) affects over 300 million people worldwide, with the hippocampus showing decreased volume and activity in patients with MDD. The current study investigated whether a novel preclinical model of depression, unpredictable intermittent restraint (UIR), would decrease hippocampal neuronal dendritic complexity. Adult Sprague Dawley rats (24 male, 24 female) were equally divided into 4 groups: control males (CON-M), UIR males (UIR-M), control females (CON-F) and UIR females (UIR-F). UIR groups received restraint and shaking on an orbital shaker on a randomized schedule for 30 or 60 minutes/day for two to six days in a row for 26 days (21 total UIR days) before behavioral testing commenced. UIR continued and was interspersed between behavioral test days. At the end of behavioral testing, brains were processed. The behavior is published and not part of my honor’s thesis; my contribution involved quantifying and analyzing neurons in the hippocampus. Several neuronal types are found in the CA3 subregion of the hippocampus and I focused on short shaft (SS) neurons, which show different sensitivities to stress than the more common long shaft (LS) variety. Brains sections were mounted to slides and Golgi stained. SS neurons were drawn using a microscope with camera lucida attachment and quantified using the number of bifurcations and dendritic intersections as metrics for dendritic complexity in the apical and basal areas separately. The hypothesis that SS neurons in the CA3 region of the hippocampus would exhibit apical dendritic simplification in both sexes after UIR was not supported by our findings. In contrast, following UIR, SS apical dendrites were more complex in both sexes compared to controls. Although unexpected, we believe that the UIR paradigm was an effective stressor, robust enough to illicit neuronal adaptations. It appears that the time from the end of UIR to when the brain tissue was collected, or the post-stress recovery period, and/or repeated behavioral testing may have played a role in the observed increased neuronal complexity. Future studies are needed to parse out these potential effects.
ContributorsAcuna, Amanda Marie (Author) / Conrad, Cheryl (Thesis director) / Corbin, William (Committee member) / Olive, M. Foster (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12