Although spatial navigation is predominantly guided by allothetic visual cues, idiothetic cues can obtain control when familiar visual cues are not available. In path integration, the current position and orientation are estimated and continuously updated using idiothetic cues, which are contributed by the vestibular system. Previous studies have revealed that vestibular lesioned rats were significantly impaired in path integration. Rats assessed in the current study received neonatal treatment with either VU0240551 (KCC2 blocker) or muscimol (GABAA receptors agonist) in the vestibular nuclei. Path integration ability appears to be intact in rats receiving either treatment. However, VU0240551-treated rats displayed impairments in their ability to resolve conflicting allothetic and idiothetic cues. Therefore, it is proposed that the ability to properly resolve a cue-conflict requires the normal polarity of GABA and/or glycine action in the vestibular nuclei during the neonatal period. / published_or_final_version / Physiology / Master / Master of Medical Sciences

Benzodiazepine (BZ) drugs, such as diazepam (Valium®) and chlordiazepoxide (Librium®), are widely prescribed for their sedative/anxiolytic properties but also impair mnemonic processes in both humans and animals. In the Morris water maze, an aversively motivated spatial learning task, BZs impair spatial learning but spare retention/performance. This spatial learning deficit cannot be attributed to sedation, gross sensorimotor impairments, hypothermia, state-dependent learning, or reductions of escape motivation (anxiolysis). The following series of experiments sought to further characterize the neurochemical, neuroanatomical, and electrophysiological substrates of BZ-induced impairments of spatial learning. In Experiment I, the role of endogenous BZs in spatial learning was assessed. The BZ receptor antagonists flumazenil (Ro 15-1788) and CGS 8216, as well as the BZ receptor inverse-agonist β-carboline, enhanced spatial learning in an inverted-U dose-dependent manner, suggesting that endogenously released BZs impede optimal learning. In Experiment II, the role of the BZ ω1 receptor subtype in spatial learning was assessed. CL 218,872, a selective agonist for the BZ ω1 receptor subtype, impaired spatial learning in a dose-dependent and flumazenil-reversible manner, thereby implicating the ω1 receptor subtype in BZ-induced amnesia. Together these results suggest that endogenous BZs activity, like BZ drugs, is detrimental to spatial learning and that specific BZ receptors mediate this impairment. Several neurochemical systems are important for spatial learning in the MWM and arc influenced by BZs. The contributions of two of these neurochemical systems, the opioids and acetylcholine (ACh), to the spatial learning deficit produced by BZs were assessed. In Experiment III, a better understanding of the role of opioid systems in spatial learning was sought. Morphine, a prototypical opioid, impaired spatial learning in a dose-dependent and naloxone-reversible manner. However, morphine also impaired performance and escape to a visible platform and its effects on spatial learning could be attenuated by increasing the escape incentive (colder water). This impairment pattern suggests that morphine impairs spatial learning by reducing escape motivation. Because both BZs and cold water immersion increase endogenous opioid activity, it seemed possible that the combination of drug- and water-induced opioid release might mediate the spatial learning deficit produced by BZs. In Experiment IV, naloxone, an opioid receptor antagonist, completely blocked the spatial learning deficit produced by morphine but failed, even at a higher dose, to block the spatial learning deficit produced by diazepam . Conversely, flumazenil, a BZ receptor antagonist, completely blocked the spatial learning deficit produced by diazepam but failed to affect the amnesic effects of morphine. Together, these findings strongly suggest that the spatial learning deficit produced by BZs is not due to enhanced opioid activity. There is also biochemical evidence that BZs interact with ACh systems. In Experiment V, flumazenil attenuated the spatial learning deficit produced by scopolamine, an ACh (muscarinic) antagonist, but physostigmine, an acetylcholinesterase inhibitor, failed to attenuate the spatial learning deficit produced by chlordiazepoxide, even at doses that completely reversed the spatial learning deficit produced by scopolamine. Together these results fail to support the notion that BZs impair spatial learning by reducing ACh activity but suggest that scopolamine impairs spatial learning by enhancing endogenous BZ activity. Several neuroanatomical regions possess a high density of BZ receptors and are also integral for spatial learning in the MWM. In Experiment VI, infusions of chlordiazepoxide into the medial septum, but not frontal cortex, nucleus basalis magnocellularis, amygdala, hippocampus, or cerebellum, impaired spatial learning but had little effect on anxiety. Conversely, infusions of chlordiazepoxide into the amygdala reduced anxiety but had little effect on spatial learning. These results suggest that the medial septum mediates the amnesic effects of BZs and that the amygdala mediates the anxiolytic effects. In Experiment VII, intraseptal infusions of chlordiazepoxide were additionally found to impair spatial learning in a dose-dependent and flumazenil-reversible manner. However, infusions of flumazenil into the medial septum failed to block the amnesic effects of systemically administered chlordiazepoxide, suggesting that the amnesic to effects of BZs are not mediated by the medial septum exclusively. Tetrahydroaminoacridine, an acetylcholinesterase inhibitor, failed to attenuate the spatial learning deficit produced by intraseptal infusions of chlordiazepoxide, suggesting that the deficit was not due to a disruption of the septohippocampal ACh projection. Together, these results suggest that chlordiazepoxide impairs spatial learning by interacting with the septohippocampal GABAergic projection. The septohippocampal GABAergic projection regulates the excitability of hippocampal afferents (e.g., perforant path). Experiment VIII assessed the effects of systemically administered BZs on the induction of long-term potentiation (LTP) in the perforant path. CL 218,872, but not chlordiazepoxide or diazepam , significantly suppressed long-term potentiation. However, all drugs impaired spatial learning. These findings suggest that CL 218,872 impairs spatial learning by suppressing LTP but that BZ-induced spatial learning deficits can occur in the absence of perforant path LTP suppression. Taken together, the above results suggest that endogenous BZ systems, particularly those in the septohippocampal system, are important modulators of mnemonic processes. These findings are discussed in the context of understanding information storage processes and the implications for clinical populations. / Graduate

Thesis (Ph. D.)--Oregon State University, 2008. / Printout. Includes bibliographical references. Also available on the World Wide Web.

When different development rates for psychological processes such as those in spatial memory exist, they can be linked to relevant brain areas via their different developmental rates. The hippocampus and caudate nucleus have been implicated in allocentric and egocentric spatial behavior changes found in youth and old age. Variation in allocentric and egocentric behavior in squirrel monkeys due to age was examined using a quadruple T-maze and animals in three age groups: 0.3 - 4 year olds, (n = 12), 5 - 10 year olds (n=12) and 11 - 17 year olds (n = 12). Subjects were trained to go to one of three goals in the maze from one of two training release locations. When they reached criterion for consistent responding, they were given probe trials pseudorandomly interspersed with the training trials in which they were released from one of the three other locations. The 12 test sessions were divided into three phases consisting of four sessions each. A 3 (age groups) x 3 (probe sites) x 3 (phases) mixed design ANOVA with repeated measures on the second and third factors revealed only a significant effect for probe site (F(1,33) = 14.55, p < .01) sing the Geisser-Greenhouse correction for heterogeneity of variance. The pattern of responding most clearly resembled route and was stable over testing. Age was not significant although there was a trend toward random behavior in young and more route-like behavior in older animals. Intrinsic maze cues effects on responding were examined. These data were analyzed using a 3 (age groups) x 2 (training groups) x 3 (probe sites) mixed design ANOVA with repeated measures on the last factor, and again revealed only a significant probe site effect (F(1,33) = 14.55, p < .01). Thus cues intrinsic to the maze did not affect response pattern. Only 13 subjects clearly used one of the three spatial strategies: 6 route, 3 direction, and 4 place. Of the remaining 23 animals 11 were young, 5 were adult and 7 were mature. Two used a variation of place, three used a combination of strategies, four were idiosyncratic, 10 used proto-route (route-like, but not systematic enough to be route) and three were random. The use of place strategy by animals as young as 4 and as old as approximately 17 implicates hippocampal changes occurring outside this age range.

Thesis (M.S.)--Marshall University, 2003. / Title from document title page. Document formatted into pages; contains v, 91 p. including maps and illustrations. Includes bibliographical references (p. 39).

Behavioural, electrophysiological, and anatomical evidence suggests that retrosplenial (RS) cortex (areas RSA and RSG) plays a role in spatial navigation. It has been recently suggested that it is damage to the underlying cingulum bundle (CG) (areas CG and IG), and not RS, tht disrupts spatial place learning. I revisited this issue by comparing the rat strains and lesions used in studies that typically report RS deficits, to those used in studies in which no RS deficit is reported. I found both selective RS damage and selective CG damage to disrupt spatial behaviour, suggesting independent contributions to spatial learning and memory from both of these structures. Further, previous failures to find RS deficits are shown to be the result of an inappropriate choice of rat strain for studying normal brain-behaviour relationships combined with a failure to use appropriate testing methods for assessing spatial behaviour. / x, 134 leaves : ill. ; 28 cm.

Thesis (M.S.)--Villanova University, 2009. / Psychology Dept. Includes bibliographical references.

Thesis (Ph. D.)--Oregon State University, 1994. / Typescript (photocopy). Includes bibliographical references (leaves 108-121). Also available on the World Wide Web.

The present study, in contrast with previous work that has isolated one or two important factors influencing the status of the zoo, considered the three important zoo reference groups--animals, visitors, and staff members--and their interrelationships within the zoo environment. Two approaches were used to investigate the system of interactions within the zoo. First, an in-depth examination of a new set of naturalistic exhibits was performed. Second, a comparison of two of these naturalistic exhibits with two older, sterile exhibits which housed the same species at the same zoo was made. Multiple methods were used in the present study and included behavior mapping of visitors, staff, and animals, timing of visitor stays at exhibits, tracking of visitors through the exhibits, a visitor questionnaire, and interviews with staff members. One major finding was the lack of correspondence among the major groups as to the acceptability of exhibits. For example, one exhibit which was considered beneficial to the enclosed animals and was well utilized and positively evaluated by visitors presented staff members with great difficulties in animal containment and exhibit maintenance. Comparisons of naturalistic enclosures and sterile cement enclosures housing the same species revealed no consistent, clear-cut differences in animal and visitor behavior, however, attitudinal differences were found for staff members and visitors. Visitors and staff members preferred the naturalistic exhibits and perceived them as more beneficial to animals and visitors. These findings were discussed in terms of theoretical and applied issues relevant to zoo design and management and to research in zoos.

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