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Thesis (Ph.D. in Human Medical Genetics) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 141-157). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (Ph.D.)--Uniformed Services University of the Health Sciences, 2006 / Typescript (photocopy)

Previous studies have shown that fish release alarming substances into the water to alert their kin to escape from danger. In our laboratory, we found that zebrafish produce trypsin and release it from their gills into the environment when they are under stress. By placing the zebrafish larvae in the middle of a small tank and then placing trypsin at one end of the tank, we observed that the larvae moved away from the trypsin zone and almost to the opposite end of the tank. This escape response was significant and did not occur in response to the control substances, bovine serum albumin (BSA), Russell's viper venom (RVV), and collagen. Also, previously, we had shown that the trypsin could act via a protease-activated receptor-2 (PAR2) on the surface of the cells. Therefore, we hypothesized that trypsin would induce a change in neuronal activity in the brain via PAR2-mediated signaling in cells on the surface of the fish body. To investigate whether the trypsin-responsive cells were surface cells, we generated a primary cell culture of zebrafish keratinocytes, confirmed these cells' identity by specific marker expression, and then incubated these cells with the calcium indicator Fluo-4 and exposed them to trypsin. By using calcium flux assay in a flow-cytometer, we found that trypsin-treated keratinocytes showed an increase in intracellular calcium release. To test whether PAR2 mediates the escape response to trypsin, we treated larvae with a PAR2 antagonist and showed that the trypsin-initiated escape response was abrogated. Furthermore, par2a mutants with knockdown of par2a by the piggyback knockdown method failed to respond to trypsin. Trypsin treatment of adult fish led to an approximately 2-fold increase in brain c-fos mRNA levels 45 mins after trypsin treatment, suggesting that trypsin signals may have reached the brain, probably via a spinothalamic pathway. Taken together, our results reveal a novel trypsin-initiated escape response in fish. These studies should enhance our understanding of fish communication in general and alarm behavior in particular. Furthermore, since pain receptors in other animals are also PAR2, our finding may be useful in exploring pathways of pain reception.

Previous studies have reported that spontaneous startles occur most frequently in the quiet sleep states, and have posited an energy release model in which spontaneous startles occur to release energy which would otherwise wake the infant. An alternative suggestion is that startles serve a homeostatic function by increasing the activity of the infant during periods of low arousal. The purpose of the current study was to examine the function of spontaneous startles using the ongoing cardiac and respiratory activity as indices of arousal. Twenty-six newborn infants were assigned to two groups. The first group was exposed to auditory stimulation which previously had been shown to decrease heart rate and respiratory rate for the first half of the one hour observation period. To the extent that spontaneous startles are related to periods of low arousal, decreasing the ongoing activity via the auditory intervention was expected to increase the rate of startles. The second group received no auditory stimulation. The occurrence of spontaneous startles was preceded by periods of lower than average heart rate and decreasing respiratory rate. Startles were followed by periods of increasing heart rate and further decreasing respiratory rate. In addition, the auditory intervention group reliably showed both a lower heart rate and an increased number of startles while exposed to the auditory stimulation, while the nonintervention group showed comparable rates of startles and heart rates in both halves of the observation period. Further, regardless of group status, most infants had their higher rate of startles in the period in which they had their lower heart rate. Finding lower heart rate and decreasing respiratory rate preceding startles, and lower heart rate and increased number of startles when exposed to the auditory stimulation, suggests that spontaneous startles modulate periods of low arousal in newborn infants. / Ph. D.

The decline of the Oregon Spotted Frog (Rana pretiosa), a Pacific Northwest endemic now federally listed as threatened, has been attributed to several aspects of ecosystem alteration, primarily habitat degradation and loss. The introduced American Bullfrog (Rana (Aquarana) catesbeiana) has been widely implicated in those declines, but the basis of that contention has been difficult to characterize. The bullfrog occurring at every site of recent Oregon Spotted Frog extirpation has focused concern about its impact. Here, I present a suite of interconnected studies that examine the behavioral ecology of both species to better understand the potential for bullfrog-mediated Oregon Spotted Frog extirpation. I quantified Oregon Spotted Frog anti-predator behavior from the only known population successfully co-occurring with bullfrogs (Conboy Lake) and a population devoid of bullfrog impact (Big Marsh), and compared these behaviors to the predatory traits of the bullfrog. The initial study revealed that captive-reared individuals from the Oregon Spotted Frog population that has successfully co-occurred with bullfrogs respond faster to a predatory stimulus (measured as latency to response) than Oregon Spotted Frogs from a population not to exposed to bullfrogs. Subsequent field investigations of the approach distance allowed by a predator stimulus before taking evasive action (termed the flight initiation distance: FID) conducted with the Oregon Spotted Frog population co-occurring with bullfrogs first demonstrated that FID of recently metamorphosed bullfrogs is consistently greater than that of recently metamorphosed Oregon Spotted Frogs. Further, examination of FID across all post-metamorphic age classes of Oregon Spotted Frogs revealed that older frogs do not allow as close approach as recently metamorphosed Oregon Spotted Frogs. This age class shift in FID did not occur in the Oregon Spotted Frog population not exposed to bullfrogs. In the latter population, FID did not differ among age classes. Since the bullfrog might be driving this age-based change in anti-predator behavior, I explored the variation in strike distance of bullfrogs from the site of co-occurrence in both the field and laboratory to determine the extent of overlap with Oregon Spotted Frog FID. I found that the bullfrog strike distance significantly overlaps the FID of all ages of Oregon Spotted Frogs from the bullfrog-free site but only that of youngest (recently metamorphosed) frogs at the site of co-occurrence. Older Oregon Spotted Frogs from the site of co-occurrence generally escaped at distances greater than the strike distance of bullfrogs. I also collected > 880 bullfrogs from the site of co-occurrence and analyzed the stomach contents to assess their dietary trends. I found that bullfrogs consume Oregon Spotted Frogs at the site, but do not eat the larger (older) frogs. Moreover, the body size ratio between Oregon Spotted Frogs as prey and bullfrogs as predators suggests that nearly all of the adult size distribution of bullfrogs at Conboy would be incapable of preying on adult Oregon Spotted Frogs. Collectively, these studies strongly suggest that bullfrogs have altered the escape behavior of Oregon Spotted Frogs at Conboy Lake and that most adult Oregon Spotted Frogs at Conboy may have a size-based release from predation by bullfrogs. Implicit in this finding is that bullfrogs may pose a real threat via predation to other Oregon Spotted Frog populations with which they might come into contact where the distribution of bullfrog body sizes differ substantially from that at Conboy Lake.

Title from PDF of title page. / Document formatted into pages; contains 18 pages. / Thesis (Au.D.)--University of South Florida, 2003. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: This study examined the effects of genetic background on the acoustic startle response (ASR) and its modulation by prepulse inhibition (PPI) by comparing nine inbred strains of mice. The ASR, a jerk-like motor reflex, is elicited by bursts of noise or tones with sound pressure levels of 80-90 dB and greater. PPI is a type of modulation of the ASR, requires no training, and results in observable response in both mice and humans. Data were obtained from nine inbred mouse strains, sixteen per strain, which were shipped at approximately 3-5 weeks old from The Jackson Laboratory. In general, ASRs were generally smaller when the startle stimulus was less intense. PPI was relatively weak for the 4 kHz prepulse, and stronger with prepulses of 12 kHz and 20 kHz. However, means varied widely across strains for both ASR and PPI, suggesting a strong influence of genetic background on these behaviors. / ABSTRACT: In addition to genetic influences, peripheral hearing loss and central auditory processing factors must be taken into consideration. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.

Background. Various studies show that cannabis use alters attention and cognitive functioning in healthy humans and may contribute to development of schizophrenia or worsening of pre-existing psychosis. However, the impact of cannabis use on brain function in humans is not well understood. Schizophrenia is associated with a deficit in prepulse inhibition (PPI), the normal inhibition of the startle reflex by a non-startling stimulus (prepulse), presented before the startle stimulus at short time intervals (lead-time intervals). Such PPI deficit is thought to reflect a sensorimotor gating dysfunction in schizophrenia. PPI is also modulated by attention and PPI reduction in schizophrenia is observed when patients are asked to attend to, not ignore, the stimuli producing PPI. The aim of the current study was to investigate the association between self-reported chronic cannabis use and attentional modulation of PPI in healthy controls and in patients with schizophrenia. Furthermore, the association between cannabis use and other startle reflex modulators, including prepulse facilitation (PPF) of the startle reflex magnitude at long lead-time intervals, prepulse facilitation of the startle reflex onset latency and habituation of the startle reflex magnitude, were examined. Method. Auditory-evoked electromyographic signals were recorded from orbicularis oculi muscles in chronic cannabis users (29 healthy controls and 5 schizophrenia patients) and non-users (22 controls and 14 patients). The data for 36 participants (12 non-user controls, 16 healthy cannabis users, and eight non-user patients) were used in the final analyses and the patient data were used as a pilot study, because relatively few participants met the rigorous exclusionary criteria. Participants were instructed to attend to or to ignore either the startle stimuli alone (70 100 dB) or prepulse (70 dB) and startle stimuli (100 dB) separated by short lead-time intervals (20 200 ms) and long lead-time intervals (1600 ms). In order to ignore the auditory stimuli the participants played a visually guided hand-held computer game. A pilot study showed that the response component of playing the game had no effects on attentional modulation of the startle reflex magnitude and onset latency. Results. Relative to controls, cannabis use in healthy humans was associated with a reduction in PPI similar to that observed in schizophrenia while attending to stimuli, and with an attention-dependent dysfunction in the startle reflex magnitude habituation. While ignoring the stimuli there were no statistical differences in PPI between cannabis users and controls, although PPI in cannabis users tended to differ from that of the patients. The reduction in PPI in cannabis users was correlated with the increased duration of cannabis use, in years, but not with the concentration of cannabinoid metabolites in urine or with the recency of cannabis use in the preceding 24 hours. Furthermore, cannabis use was not associated with any differences in PPF, onset latency facilitation, and startle reflex magnitude in the absence of prepulses. The accuracy of self-reports of substance use was also investigated in this study and was found to be excellent. In addition, the study examined the validity of the substance use module of the diagnostic interview, CIDI-Auto 2.1, which was found to be acceptable for cannabis misuse diagnoses (abuse and/or dependence). Finally, cannabis dependence was found to be associated with more diagnoses of mental illness other than schizophrenia (mainly depression). Conclusions. The results of the current study suggest that chronic cannabis use is associated with schizophrenia-like deficit in PPI in otherwise healthy humans. This PPI reduction is associated with attentional impairment rather than a global sensorimotor gating deficit in healthy cannabis users.

Effects of Toxoplasmosis on Reaction Times and Prepulse Inhibition of Startle Reaction in Humans vi Abstract Toxoplasma gondii, a single-cell coccidia from almost exclusively parasitic phylum Apicomplexa, does not typically cause acute health issues in humans with most exceptions among immunodeficient individuals and pregnant mothers or, more precisely, their offspring. In the latent phase, the bradyzoites in tissue cysts placed most often in neural and muscle tissues can evolve pressure on the host's body both as a collateral effect of the presence of the parasitic organism in host's tissues and as a consequence of adaptive evolution leading to increase in probability of trophic transmission to the final host, a felid. In humans, this can result in slight changes in personality profiles, deterioration of psychomotor and cognitive functions, and development of serious mental disorders. The thesis focuses predominantly on one of the aspects of the changes, namely the effect of latent toxoplasmosis on the processing of startle signals themselves and when modified by a preceding low-intensity signal; this processing may be connected with the development of schizophrenia in predisposed individuals. Studies conducted within the project framework found changes int the speed of signal processing in...

Thesis (Ph. D.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).