Thesis (Ph.D.)--University of Delaware, 2009. / Principal faculty advisor: . Includes bibliographical references.

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

The posterior parietal cortex (PPC) is a cortical region receiving inputs from different sensory modalities which has been shown to subserve a visuospatial function. The potential contribution of PPC in audiospatial behaviours and recognition of amodal spatial correspondences were postulated and assessed in the present study. Adult male Long- Evans rats received PPC lesions by aspiration, and they were compared to sham operated control rats on three behavioural tasks. In the Morris water maze, the rats had to learn to use the distal visual cues to locate an escape platform hidden in the pool. In an open field task, the rats were assessed on their reactions to a spatial relocation of a visual or an auditory object. In a spatial cross-modal transfer (CMT) task (Tees & Buhrmann, 1989), rats were trained to respond to light signals using spatial rules, and were then subjected to transfer tests using comparable sound signals. Results from the Morris water maze, the open field, and the initial training phase of the spatial CMT task confirmed a visuospatial deficit in PPC lesioned rats. However, if given sufficient training, PPC lesioned rats could learn the location of a hidden platform in the Morris water maze, and they could also acquire spatial rules in the CMT task. Such results indicated that the visuospatial deficits in PPC lesioned rats were less severe than previously thought. On the other hand, a persistent navigational difficulty characterized by a looping pattern of movement was observed in the PPC lesioned rats in the Morris water maze. Results from the open field indicated that PPC was less involved in audiospatial behaviours. Moreover, results also indicated that PPC was not necessary for spatial CMT. Hence, data from the present study did not support the idea that PPC played an essential role in supramodal spatial abilities in the rats. Instead, data from the spatial CMT task seemed to imply a role of PPC in managing conflicting spatial information coming from different sensory modalities.

No description available.

Dissertation (Ph.D.)--Auburn University, 2007. / Abstract. Includes bibliographic references.

Univ., Habil.-Schr.--Mannheim, 2002.

Dissertation (Ph.D.)--University of Toledo, 2004. / Typescript. "A dissertation [submitted] as partial fulfillment of the requirements of the Doctor of Philosophy degree in Engineering." Bibliography: leaves 194-211.

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

This study used the process dissociation procedure to investigate the effects of three variables on conscious and unconscious influences of memory for object location. The purpose was not only to provide insight into conscious and unconscious influences of memory for object location, but also to obtain support for the assumption that the two influences operate independently. Such support can be obtained by demonstrating that a manipulation affects one component of memory but leaves the other invariant. The three variables used in the present study included dividing attention at study and test, the age of the participants, and habit strength. In the first experiment, when attention was divided at study, the conscious estimate was significantly reduced under conditions of divided attention. This result was also found when attention was divided at test, although the effect only approached significance. Moreover. when attention was divided at study, there was a tendency for the unconscious estimate to be greater under full attention than under divided attention. When attention was manipulated at test, however, the unconscious estimate did not vary across the two attention conditions. The results of Experiment 1, therefore, did not provide strong evidence for the assumption of independence. Such evidence, however, was obtained in Experiments 2 and 3 where a double dissociation between conscious and unconscious influences of memory for object location was observed. Specifically, in Experiment 2 it was found that age affected the conscious component but left the unconscious component invariant, whereas in Experiment 3 it was found that manipulating habit strength affected the unconscious influence of memory for spatial location but not the conscious influence. The results of these experiments are discussed in terms of their importance for research on memory and aging and systems theories of memory, as well as for the assumption that conscious and unconscious influences of memory operate independently. / Graduate

The posterior parietal cortex (PPC) is a cortical region receiving inputs from different sensory modalities which has been shown to subserve a visuospatial function. The potential contribution of PPC in audiospatial behaviours and recognition of amodal spatial correspondences were postulated and assessed in the present study. Adult male Long- Evans rats received PPC lesions by aspiration, and they were compared to sham operated control rats on three behavioural tasks. In the Morris water maze, the rats had to learn to use the distal visual cues to locate an escape platform hidden in the pool. In an open field task, the rats were assessed on their reactions to a spatial relocation of a visual or an auditory object. In a spatial cross-modal transfer (CMT) task (Tees & Buhrmann, 1989), rats were trained to respond to light signals using spatial rules, and were then subjected to transfer tests using comparable sound signals. Results from the Morris water maze, the open field, and the initial training phase of the spatial CMT task confirmed a visuospatial deficit in PPC lesioned rats. However, if given sufficient training, PPC lesioned rats could learn the location of a hidden platform in the Morris water maze, and they could also acquire spatial rules in the CMT task. Such results indicated that the visuospatial deficits in PPC lesioned rats were less severe than previously thought. On the other hand, a persistent navigational difficulty characterized by a looping pattern of movement was observed in the PPC lesioned rats in the Morris water maze. Results from the open field indicated that PPC was less involved in audiospatial behaviours. Moreover, results also indicated that PPC was not necessary for spatial CMT. Hence, data from the present study did not support the idea that PPC played an essential role in supramodal spatial abilities in the rats. Instead, data from the spatial CMT task seemed to imply a role of PPC in managing conflicting spatial information coming from different sensory modalities. / Arts, Faculty of / Psychology, Department of / Graduate