Physiology

The human prefrontal cortex (PFC) is associated with complex cognitive behaviors such as planning for the future, memory for serial order, social information processing and language. Understanding how the PFC has changed through time is central to the study of human neural evolution. Here we investigate the expansion of the PFC by measuring relative surface area of the PFC in Pan troglodytes and Homo sapiens. Magnetic resonance images (MRI's) from 8 preserved chimpanzee brains (3 male and 5 female adults) were segmented and measured. The results of this study indicate that there are gross anatomical differences between the chimpanzee and human prefrontal cortex beyond absolute size. The lower surface area to volume ratio in PFC of the chimpanzee when compared to a human indicates less gyral white matter in this region and thus, less associative connectivity. This anatomical evidence of a difference corresponds with the lesser cognitive complexity observed in chimpanzees.

The central importance of vision to an organism is evident in the anatomical and physiological adaptations within the eye that can be correlated to the organism's behavior and ecology. The goal of this study was to perform a functional analysis of adaptations within the elasmobranch visual system. An integrative approach was used to examine morphological and physiological adaptations in several species and link these adaptations to phylogeny, locomotion, habitat, behavior and ecology. Functional aspects investigated were eye position, pupil shape, spectral sensitivity, temporal resolution, the extent of the visual field and ultimately the integration of the visual and electrosensory systems. The elasmobranch eye adapts to the light environment of its habitat. Sharks from similar habitats had similar spectral sensitivities such as the bonnethead and blacknose sharks, both maximally sensitive to blue light of 480 nm. The spectral sensitivity of the scalloped hammerhead, which lives in a different environment, was maximally sensitive to green light (530 nm). The temporal characteristics of the eye also matched habitat and lifestyle. Species experiencing variable light conditions exhibited increased critical flicker-fusion frequencies, such as the bonnethead (31 Hz) and scalloped hammerhead (27 Hz), in contrast to deeper or more nocturnal species such as the blacknose shark (18 Hz). Elasmobranch visual fields correlated to each species' lifestyle, habitat and foraging strategy. Expansive monocular views, including a 360° panoramic view in the yellow stingray, were measured in species that rely on vision for vigilance against predators.

Experimentally naive rats exhibit varying degrees of novelty exploration. Some rats display high rates of locomotor reactivity to novelty (high responders; HR), and others display low rates (low responders; LR). The novelty-seeking phenotype (LRHR) is introduced as a model of stress responsiveness. In this thesis I examined effects of chronic variable physical and social stress or control handling on the levels of various neurotrophins in the hippocampus, and changes in mossy fibre terminal fields in LRHR rats. A positive correlation is seen between histone deacetylase 2 and brain-derived neurotrophic factor (BDNF) levels both of which are oppositely regulated in LRHR CA3 fields in response to chronic social stress. Increase in BDNF levels in CA3 field accompanied increase in supra-pyramidal mossy fibre terminal field size (SP-MF) in HRs, and decrease in BDNF levels accompanied decrease in SP-MF volume in LRs. Epigenetic regulation of neurotrophic support underlying these structural changes is discussed.

In light of exceptionally delayed reproductive senescence exhibited by a 64 year old female chimpanzee (Pan troglodytes) housed in Florida, endocrinal analyses meant to determine the state of her current reproductive viability were conducted. Urine was collected from the study subject for a period of 88 days spaced within an interim of roughly 6 months and the specimens were sent to the Hominoid Reproductive Ecology Laboratory for assessment. Additional data was collected from three control females in order to provide a basis of comparison against the hormonal markers present in the geriatric study animal. Results indicate that the geriatric female does not presently appear to be cycling, but nor does she exhibit signs of complete reproductive cessation. This could signify that Pan troglodytes adheres to a pattern of reproductive aging not necessarily shared by Homo sapiens, which has further implications for the evolutionary trajectory of menopause in the human female.

Serotonin (5-HT) is a neurotransmitter in the central nervous system. Decrease in the brain 5-HT level could induce depression, showing a state of low mood, aversion to motion and feeling of worthlessness. About 12 million adults in the United States have depression. Antidepressants, such as monoamine oxidase inhibitors and selective serotonin reuptake inhibitors, can alleviate the depressive mood by increasing the brain's 5-HT activity, however they can also induce a potentially life-threatening side effect, namely 5-HT syndrome. This syndrome is manifested by neuromuscular hyperactivities, mental disorders and autonomic dysfunctions. Clinical studies have demonstrated that 5-HT2A receptor antagonists could effectively block severe symptoms of patients with the 5-HT syndrome. To understand the underlying mechanisms, in this study we examined the activity of the 5-HT2A receptor in rats with the 5-HT syndrome evoked by a combined injection of clorgyline, a monoamine oxidase inhibitor , and paroxetine, a selective 5-HT reuptake inhibitor. The major findings from my study were that: (1) Chronic clorgyline treatment significantly exacerbated 5-HT2A receptor-mediated symptoms of the 5-HT syndrome animals; (2) The 5-HT2A receptor-mediated symptoms were also aggravated when the 5-HT syndrome animals were housed in warm (32 ÀC) ambient temperature; (3) Blocking 5-HT2A receptors in the medial prefrontal cortex alleviated the 5-HT syndrome through a circuit between raphe serotonergic neurons and medial prefrontal cortex glutamatergic neurons. Taken together, my data demonstrate that the activity of 5-HT2A receptors may be enhanced by chronic antidepressant treatment and warm environmental temperature.

In sea turtles, the study of the etiology and development of fibropapillomatosis is not fully understood. Sea turtle fibropapillomatosis is a disease characterized by the proliferation of skin fibropapillomas and occasional internal fibromas. In this study, sea turtle fibropapilloma tumor and healthy tissue samples were used to look at VEGF, BCL-2 and Bax expression. Cancer tumors have a well established pattern of protein expression that involves overexpression of vascular endothelial growth factor (VEGF), responsible for the growth of new blood vessels, and a high BCL-2 to Bax ratio that leads to uncontrolled cell proliferation. Real time PCR was used to analyze VEGF expression, and Western blot techniques were used to measure BCL-2 and Bax expression. The results indicated that expression of VEGF was not significantly higher in tumor vs. skin tissue. For the differential expression of BCL-2 and Bax, the results were not in agreement with the established levels found in cancer studies, showing no significant change in BCL-2 expression and significantly higher levels of Bax in tumor vs. healthy tissue.

Although it is well known that the pupil responds dynamically to changes in ambient light levels, the results from this dissertation show for the first time that the pupil also responds dynamically to changes in spatially distributed attention. Using a variety of orientating tasks, subjects alternated between focusing attention on a central stimulus and spreading attention over a larger area. Fourier analysis of the fluctuating pupil diameter indicated that: 1) pupil diameter changed at the rate of attention variation, dilating with broadly spread attention and contracting with narrowly focused attention, and 2) pupillary differences required changes in attentional spread; there were no differences in pupil diameter between sustained broad and sustained spread attention. Given that broadly spread attention increases the relative activation of large receptive fields and narrowly focused attention increases the relative activation of small receptive fields (Balz & Hock, 1997), the results of this study indicate that these attentional effects on receptive field activation can be mediated by changes in pupil diameter. That is, under broad attention, the corresponding pupillary dilation observed would increase spherical aberration, blurring the image thereby reducing high spatial frequency information and decreasing the activation of relatively small cortical receptive fields compared to relatively large receptive fields. This increased perception of low spatial frequencies would be beneficial in cases where attention is spread over a large area. Alternatively, under narrow attention the resulting pupillary constriction reduces spherical aberration sharpening the image and preserving high spatial frequency information resulting in a relatively increased response of small receptive fields.

Mammalian neurons exhibit extreme sensitivity to oxygen deprivation and undergo rapid and irreversible degeneration when oxygen supply is curtailed. Though several neuroprotective pathways are activated during oxygen deprivation, their analyses are masked by the complex series of pathological events which are triggered simultaneously. Such events can be analyzed in the anoxia tolerant fresh water turtle, which can inherently survive the conditions of oxygen deprivation and post-anoxic reoxygenation without brain damage. It is likely in such a model that modulation of a particular molecular pathway is adaptive rather than pathological. The major objective behind this study was to analyze the intracellular signaling pathways mediating the protective effects of adenosine, a potential neuromodulator, and its effect on cell survival by influencing the key prosurvival proteins that prevent apoptosis. In vivo and in vitro studies have shown that adenosine acts as a neuroprotective metabolite and its action can be duplicated or abrogated using specific agonist and antagonists. Stimulating the adenosine receptors using selective A1 receptor agonist N6-cyclopentyladenosine (CPA) activated the presumed prosurvival ERK and P13-K/AKT cascade promoting cell survival, and suppression of the receptor using the selective antagonist DPCPX (8- cyclopentyl-1,3-dipropylxanthine) activated the prodeath JNK and P38 pathways. The complex regulation of the MAPK's/AKT signaling cascades was also analyzed using their specific inhibitors. The inhibiton of the ERK and AKT pathway increased cell death, indicating a prosurvival role, whereas inhibiton of the JNK and p38 pathway increased cell survival in this model. In vitro studies have also shown a high Bcl-2/BAX ratio during anoxia and reoxygenation, indicating a strong resistance to cell death via apoptosis.

Posthatchling green (Chelonia mydas) and loggerhead (Caretta caretta) turtles overlap ecologically but differ morphologically. This study compared hydrodynamic stability between the two species during swimming to test for functional differences in body shape. Flipper movement paths, four stability measures (yaw, pitch, heave, and sideslip), and the relative positions of the centers of buoyancy and gravity were compared between species. Both centers of buoyancy and gravity lie in the anterior body; their positions relative to one another differed with species, but showed no functional consequences. Neither species demonstrated substantial yaw, sideslip, or pitch. Both experienced upward heave with the flippers' downstroke and downward heave with the upstroke; however phase relationships differed between these limb and body motions. No differences were found between the two species. Despite obvious morphological differences, loggerheads and green turtles were similarly stable during swimming, suggesting that the species use different mechanisms to achieve stability.

Serotonin syndrome (SS) is a drug-induced toxicity caused by an excess of serotonin (5-HT) in the central nervous system (CNS). The symptoms of the disorder range from mild to severe, with the severe state evoking life-threatening hyperthermia. Autonomic dysfunction is controlled in part by serotonin receptors, with the 5-HT2A receptor responsible for increasing core body temperature (Tcor). Our results show that the 5-HT2A receptors on the preoptic/anterior hypothalamus (PO/AH) and prefrontal cortex (PFC), in particular, are sensitive to changes in ambient temperature (Tamb). The toxic increase of 5-HT is postulated to occur due to the temperature-dependent activation of these receptors that promotes a positive feedback mechanism. Our results suggest that changes in Tamb can either exacerbate or alleviate the symptom and that this is mediated by the 5-HT2A receptors. Understanding the mechanism involved in elevating Tcor is imperative in treating and preventing the disorder.