A large number of studies on both animals and humans have demonstrated that learning is influenced by context, or secondary cues that are present when an association is formed. The mechanistic aspects of context-dependent memory retrieval, or the context shift effect, have been well studied in strictly controlled laboratory settings. However, the adaptive value of attending to contextual cues in ecologically relevant situations has received considerably less attention. The goal of this dissertation is to examine the functional value of attending to context during learning. The jumping spider Phidippus princeps is capable of learning the ecologically relevant task of avoiding aposematic prey. However, when spiders were tested in an environment different from the one in which they were trained, attack rates increased and spiders no longer demonstrated retention of the association. Subsequent experiments demonstrated that spiders can use contextual cues to inform adaptive decisions about patch selection based on experience with prey of varying palatability or electric shock. Lastly, learning to avoid prey across a consistent contextual background versus a variable background produces initial differences in rates of learned avoidance, while ultimately learning performance between the groups is similar. Thus, contextual information (either in its constancy or variability) is an important component of avoidance learning in jumping spiders and can be valuable information in adaptive decision-making.

The drug ±3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational substance among young people. Most prior research has not attempted to carefully emulate human ecstasy use patterns in animal investigations. The objectives of the present series of experiments were to develop a rat model of intermittent ecstasy use and to begin to characterize the acute and long-term physiological, behavioral, and neurochemical consequences of adolescent MDMA exposure. In Experiments I and II, male Sprague-Dawley rats received 20 mg/kg/day of MDMA on every fifth day from postnatal day 35 to 60. This regimen caused subtle reductions in cortical serotonin transporter (SERT) binding and dose dependently modified indices of attention, working memory, and anxiety-like behavior. Experiment III tested whether periadolescent MDMA exposure (10 mg/kg x 2) modified the responses to a MDMA binge (5 or 10 mg/kg x 4) in young adulthood. Adolescent MDMA completely blocked the hypoactivity and SERT reductions induced by adult MDMA treatments. Importantly, developmental MDMA exposure only partially reduced the hyperthermia evoked by the binge. The pharmacokinetic profile of early (PD 35) and late (PD 60) adolescent MDMA (10 mg/kg) treatments were compared in Experiment IV. Pharmacokinetic parameters (elimination half-life, peak concentration) did not differ by age for MDMA but PD 60 animals showed lower peak concentrations of the metabolite methylenedioxyamphetamine (MDA). Finally, the goal of Experiment V was to determine if MDMA induced decreases in SERT levels mediated the behavioral consequences. Rats received the binge (10 mg/kg x 4) in combination with pretreatment with the serotonin reuptake inhibitor citalopram (10 mg/kg). Citalopram blocked SERT reductions measured one week after dosing and prevented some of the MDMA induced alterations in complex behavior. These studies reveal that: (1) repeated exposure to a clinically relevant MDMA dose can reduce cognitive function and alter affective behavior, (2) adolescent MDMA can lead to MDMA tolerance in adulthood, (3) the behavioral toxicology of MDMA may not be exclusively mediated by decreases in SERT. Overall, these findings indicate that the enduring neurobiological consequences of MDMA may not be limited to the serotonergic system and have substantial public health implications for regular ecstasy users. Keywords. Adolescence, Behavior, Memory, Serotonin transporter, Temperature, Weight

It is becoming increasingly clear that chemicals present in the environment can interfere with thyroid hormone (TH) action and signaling. This is of great concern because TH is critical for normal brain development and recent evidence suggests that the developing brain is exquisitely sensitive to perturbations in TH action. Developmental exposure to the ubiquitous environmental toxicants, polychlorinated biphenyls (PCBs), is associated with neurological deficits that may be related to ability of these chemicals to alter TH-mediated brain development by interfering with TH action. Thyroid hormone plays an important role of is on the development and maturation of white matter tracts and its glial constituents. Because PCBs are suspected of interfering with thyroid hormone (TH) signaling in the developing brain, and because TH is important in white matter development, this dissertation set-out to critically test the hypothesis that developmental exposure to PCBs alters white matter development by interfering with TH action. In testing this hypothesis, we addressed four main questions: (1) Do PCBs perturb white matter development by causing a relative state of hypothyroidism? (2) Is the severity of TH insufficiency associated with different effects on white matter? (3) Do PCBs have a TH-like effect on white matter composition? (4) Do PCBs and TH insufficiency alter white matter by affecting the same signaling networks? We focused our experiments on postnatal day 15, a time when both myelination and TH levels are at their peak during development, and effects of hypothyroidism on white matter development have been documented. We evaluated the effect of developmental exposure to the commercial PCB mixture Aroclor 1254, TH insufficiency, and TH excess on markers of oligodendrocyte and astrocytes in two white matter tracts, the corpus callosum (CC) and anterior commissure (AC). The results described in this dissertation are consistent with the idea that developmental exposure to PCBs alters white matter composition independent of ability to interfere with TH action. Furthermore, the nature of the experimental designs used in testing our hypothesis provided fundamental information on the role of TH in the differentiation of oligodendrocytes and astrocyte from common precursors.

Thesis (D.S.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / This two year cohort study involved 248 workers within the automotive industry and explored the effects of two workplace factors, e.g. overtime and assembly-line work, on behavior and cognitive performance as measured by neurobehavioral tests. Review of the occupational epidemiology literature did not reveal any studies of the effects of cumulative fatigue, as a result of long work days due to overtime, on cognitive abilities or job performance. Overtime, defined as number of hours worked greater than 8 hours per day and/or greater than 5 days per week, was calculated from company payroll records. Subjects were categorized as working a machine-paced, assembly line job based on review of their work histories and characterization of their job codes. Cross-sectional analysis of Year 1 data by multiple linear regression demonstrated that overtime worked the week before testing was significantly associated with increased response times on tasks involving simple and complex attention and executive function and an attention-requiring task of basic verbal abilities. The findings from Year 1 support the hypothesis that overtime per week results in cumulative fatigue which affects cognitive performance in the specific functional domains of attention and executive function. Machine-paced work was significantly associated with impaired performance in the areas of attention and executive function, however no significant mood changes were observed. An increased number of errors on a task of complex attention and executive function, poorer performance on a visual memory task involving attention and new learning skills, and reduced percent correct on a computerized task of attention and motor skills and on an attention-requiring task of basic verbal abilities were observed. Machine-paced work did not significantly affect the observed effects of overtime. The results suggest a different response to the strain produced by machine-paced work than that observed with overtime. Machine-paced work was predictive of a faster response time with increased errors, whereas the fatigue effects of overtime resulted in a slower time to complete a task without a decrease in accuracy. Neither overtime nor machine-paced work was associated with performance on any test in Year 2. It was suspected that fewer subjects working increased overtime hours, loss-to-follow-up, and that two of the tests associated with overtime in Year 1 were not repeated in the Year 2 battery, contributed to the difference in the findings between the two years. Further study is recommended to evaluate the proposed hypotheses regarding the effects of overtime and machine-paced work on cognitive function and to investigate the strategic response difference between overtime and machine-paced work. / 2031-01-01

No description available.

No description available.

No description available.

Note: Manuscript very warped.

Note: Title page omits author and title in manuscript. Taken from McGill University Thesis Directory.

No description available.