Thesis (Ph.D.), Memorial University of Newfoundland, 2000. / Bibliography: leaves 109-124.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (p. 256-292). Also available in print.

While episodic and spatial memory both depend on the hippocampus, opposite gender differences in these functions suggest they are partly separate, with different neural underpinnings. The anterior and posterior hippocampus differ  in structure and whole-brain connectivity, and studies point to the posterior hippocampus being more involved in spatial memory while the anterior hippocampus’ role in episodic memory is less clear. This thesis aims to explore the role of the anterior and posterior hippocampus, and associated brain regions, in episodic and spatial memory. Paper I studied gender differences in hippocampal activation underlying differences in spatial memory performance. Better performance in men was accompanied by greater right-lateralization of hippocampal activation compared to women. Paper II investigated regions of gray matter that covaried in volume with the anterior and posterior hippocampus, and whether these covariance patterns depended on gender and were related to behavior. The anterior and posterior hippocampus showed different patterns of covariance, with the anterior hippocampus covariance pattern observed in women and the posterior hippocampus covariance pattern primarily in men. Paper III considered whether the location of hippocampal recruitment in episodic memory depends on memory content. Verbal stimuli were associated with more anterior, and left-lateralized, encoding activations than pictorial stimuli, which in turn were associated with more posterior and bilateral encoding activations. This was not observed during retrieval. Paper IV investigated whether resting-state connectivity associated with the anterior and posterior hippocampus predicts episodic and spatial memory performance, respectively. Resting-state connectivity associated with the anterior, not posterior, hippocampus predicted episodic memory performance, while resting-state connectivity associated with the posterior, not anterior, hippocampus predicted spatial memory performance. This thesis lends further support to differences in function and structure between the anterior and posterior hippocampus suggesting that these two sub–segments play different roles in episodic and spatial memory. Further, it suggests that gender differences in anterior and posterior hippocampus function underlies gender differences in episodic and spatial memory, respectively. Considering the anterior and posterior hippocampus, as well as men and women, separately, is hence important when studying the effect of age and pathology on the hippocampus and associated memory functions.

Episodic simulation refers to the construction of imagined, hypothetical events that might occur in one's personal future. Damage to our capacity for episodic simulation can produce grave consequences, impairing our ability to anticipate, plan, and prepare for the future. New theoretical approaches have begun to uncover the cognitive and neural mechanisms underlying episodic simulation, but much remains to be examined. The purpose of this dissertation is to further investigate the mechanisms supporting episodic simulation as well as the functions it serves. In the first study of the dissertation I examine age-related deficits in imagining the future, remembering the past, and describing the present (Paper 1). These findings replicate known deficits in older adults in episodic simulation and memory, yet provide evidence of non-episodic processes that also shape their expression. I next examine component cognitive and neural processes that are recruited to generate imagined events (Paper 2). Distinct regions of the hippocampus were active when encoding, tracking novelty, or constructing imagined events, suggesting a multifaceted role of the hippocampus in supporting episodic simulation. Finally, I present evidence that episodic simulation and memory can be used to facilitate empathy, that is, intentions to help a person in need (Paper 3). People are more willing to help a person in need after imagining or remembering helping that individual. Furthermore, the episodic vividness of these imagined or remembered events heightened intentions to help. These findings elucidate a previously unconsidered mechanism for facilitating empathy, and, in doing so, open the possibility for a new functional account of episodic simulation. I close by discussing the promise of this line of work that aims to provide new insights into the relationship between episodic simulation, memory, and empathy. / Psychology

Prolonged, heavy consumption of alcohol produces marked neuroadaptations in excitatory neurotransmission. These effects are accelerated following patterns of intermittent heavy drinking wherein periods of heavy consumption are followed by periods of abstinence. Studies have shown that neuroadaptive changes in the glutamatergic N-methyl-D-aspartate (NMDA) receptor produces excitotoxicity during periods of withdrawal; however, upstream targets were not adequately characterized. The present studies sought to identify these targets by assessing the role of group 1 metabotropic glutamate receptors (mGluR) and intracellular calcium in promoting cytotoxicity of hippocampal cell layers in vitro. It was hypothesized that ethanol-induced activity of mGluR1-and-5 contributes to hippocampal cytotoxicity and promotes the behavioral effects of withdrawal in vivo. In order to identify and test this theory, rat hippocampal explants were co-exposed to chronic intermittent ethanol exposure with or without the addition of a group 1 mGluR antagonist to assess cytotoxicity in neuronal cell types. In a second study, adult male rodents were co-exposed to chronic intermittent ethanol exposure with or without the addition of an mGluR5 antagonist to assess the role of these receptors in the development of dependence as reflected in withdrawal behaviors. Together, these studies help to identify and screen toxicity of putative pharmacotherapies for the treatment of ethanol dependence in the clinical population.

published_or_final_version / Medicine / Master / Doctor of Medicine

Across bilaterian phyla, learning and memory allows animals to benefit from central-place foraging, return to ideal food sources, choose mates and avoid dangerous or harmful external stimuli. Although these behaviors are comparable in both vertebrate and invertebrate animals, it is unknown whether or not they are mediated by homologous brain structures. In insects, paired, lobate forebrain structures called mushroom bodies receive input from primary sensory neuropils and are necessary for learning and memory, whereas in crustaceans, this behavior is mediated by paired, compact forebrain structures called hemiellipsoid bodies. Mammalian learning and memory is mediated by the paired, horn-shaped hippocampi, which also receive sensory input and are likewise situated in the forebrain. Did these structures evolve independently along with the ability for animals to learn and remember associations and places? Alternatively, the hypothesis posited in this dissertation is that the last bilaterian ancestor already possessed the ability to learn and adapt to its environment, behavior mediated by paired forebrain structures that evolved divergently into the elaborated forms we observe in extant, crown-group taxa. This hypothesis is investigated and discussed in the following reports: 1) a review of insect brain anatomy and functional connectivity, including a description of mushroom bodies, in the context of arthropod evolution; 2) a comparison of neuroanatomy, circuitry, and protein expression between insect mushroom bodies and Malacostracan crustacean hemiellipsoid bodies, using cockroaches and Caribbean hermit crabs as representatives of their classes; 3) a deeper investigation of the fine structure of neuronal organization in the hemiellipsoid body of the Caribbean hermit crab, focusing on electron microscopical observations and comparisons to the ultrastructure of the fruit fly mushroom body; 4) a survey of four invertebrate Phyla, employing the strategy of comparing neuroanatomy and protein expression to investigate whether higher order forebrain structures in these animals were inherited from a common ancestor; 5) a comparison of neuroanatomy, connectivity, and protein expression in insect mushroom bodies and mammalian hippocampus, including a survey of PKA-Cα in these and corresponding structures across the Chordata. The total evidence suggests that a common Bilaterian ancestor possessed a center that evolved to become mushroom bodies in invertebrates and hippocampus in vertebrates.

No description available.

Synaptic transmission occurs as a result of either a spontaneous release of presynaptic vesicles or a batch release of presynaptic vesicles driven by action potentials. The physiological consequence of synaptic transmission driven by different patterns and frequencies of presynaptic stimulation has been extensively investigated. However, the physiological nature, mechanism as well as relevance of prolonged presynaptic stimulation have been poorly characterized. In this dissertation, I present three projects in which prolonged stimulation of synaptic transmission in different forms and different brain regions was studied for its effect on synaptic transmission, mechanisms and physiological relevance. In the first project, prolonged electrical stimulation (100 sec) at high frequency induced a deep synaptic depression in acute hippocampal slices, followed by a recovery of synaptic transmission after ~15 min. The deep synaptic depression was attributed to a complete depletion of presynaptic vesicle pools. In the second project, attempts were made to characterize the mechanism of nuclear activation of gene transcription induced by prolonged electrical stimulation (100 sec). Our results demonstrated that reduced inactivation of non-L-type calcium channels failed to provide calcium required for gene transcription, leaving the activation of gene transcription a selective function for L-type calcium channels. In the third project, we sought to study the physiological relevance of enhanced miniature events of inhibitory synapses induced by prolonged chemical stimulation. We showed that prolonged application (2 min) of nicotine to the striatal slice enhanced the frequency of miniature inhibitory currents that was accompanied with a reduction in the amplitude of evoked response. This reduction in the amplitude of evoked responses was ascribed to a compromised action potential invasion of presynaptic terminals possibly due to inactivation of sodium channels resulting from nicotine-induced depolarization. To summarize, prolonged stimulation of presynaptic vesicle release imposes significant influence upon neuron-to-neuron communication, with distinct mechanisms in different brain regions.

There are sex differences in degenerative disease prevalence in humans. Most models of degenerative disease use male animals. Examining female and male responses to stress may give insight into disease prevalence. Heat shock proteins are chaperones linked to damaged proteins in degenerative diseases and may be expressed differentially in females and males. My goal was to characterize the induced expression of Hsp70 and Hsp27 in the brain and heart of female and male rats. Rats were heat shocked, brains and hearts were removed 24 hours after, and western analyses were done to quantify the expression of these proteins. Immunofluorescence was used to localize Hsp70 and Hsp27 in the hippocampus. Overall, male rats have significantly greater induced expression of both Hsp70 and Hsp27 in the brain. In the hippocampus, Hsp70 was localized in blood vessels and microglia, and Hsp27 was localized in astrocytes, following heat shock.