The neural basis of the brain's ability to represent time, which is an essential component of cognition, is unknown. Despite extensive behavioral and electrophysiological studies, a theoretical framework capable of describing the elementary neural mechanisms used by biological neural networks to learn temporal representations does not exist. It is commonly believed that the underlying cellular mechanisms reside in high order cortical regions and there is an ongoing debate about the neural structures required for temporal processing. Recent experimental studies report sustained neural activity that can represent the timing of expected reward in low-level primary sensory cortices, suggesting that temporal representation may form locally in sensory areas of the cortex. This thesis proposes a theoretical framework that explains how temporal representations of the type seen experimentally can be encoded in local cortical networks and how specific temporal instantiations can be learned through reward modulated synaptic plasticity. The proposed framework asserts that the mechanism responsible for encoding the observed temporal intervals is long-term synaptic potentiation between neurons in a recurrent network. Analytical and numerical techniques are used to demonstrate that the model is sufficient to allow näive networks of both linear and non-linear neurons to encode and reliably represent durations specified by external cues during a training period. Analysis of a non-linear spiking neuron model is accomplished using a mean-field approach. The form of temporal learning described has specific implications that can be confirmed experimentally and these predictions are highlighted. Experimental support for a central component of the model is presented and all of the the results are discussed in relation to current experimental and computational work. / text

published_or_final_version / Biochemistry / Master / Master of Philosophy

No description available.

Drugs of abuse elicit dopamine release unconditionally, sensitizing the reward system to drugs and drug-associated stimuli resulting in compulsive drug-seeking and drug-taking behaviour. It has been discovered that these same dopamine neurons consistently respond to natural rewards when the reward delivery is at maximum uncertainty (50%). Reward uncertainty is a defining feature of gambling. Therefore, chronic increases in dopamine release from gambling-like stimuli could lead to sensitization of the reward pathways and contribute to gambling pathology. This study investigated the effects of repeated exposure to different probabilities of sucrose reward (0, 25%, 50%, 75%, 100%) on sensitivity to an amphetamine challenge (0.5 mg/kg) and development of sensitization after multiple amphetamine doses (5 x 1.0/kg) in Sprague–Dawley and Lewis rats. No significant group differences were found during the amphetamine challenge or amphetamine sensitization in either strain. Opportunities for improvement in the experimental paradigm and for future research are discussed.

Drugs of abuse elicit dopamine release unconditionally, sensitizing the reward system to drugs and drug-associated stimuli resulting in compulsive drug-seeking and drug-taking behaviour. It has been discovered that these same dopamine neurons consistently respond to natural rewards when the reward delivery is at maximum uncertainty (50%). Reward uncertainty is a defining feature of gambling. Therefore, chronic increases in dopamine release from gambling-like stimuli could lead to sensitization of the reward pathways and contribute to gambling pathology. This study investigated the effects of repeated exposure to different probabilities of sucrose reward (0, 25%, 50%, 75%, 100%) on sensitivity to an amphetamine challenge (0.5 mg/kg) and development of sensitization after multiple amphetamine doses (5 x 1.0/kg) in Sprague–Dawley and Lewis rats. No significant group differences were found during the amphetamine challenge or amphetamine sensitization in either strain. Opportunities for improvement in the experimental paradigm and for future research are discussed.

Thesis (Ph.D.)--University of Iowa, 2009. / Thesis supervisors: Warrne G. Darling, Michel Ladouceur. Includes bibliographical references (leaves 116-131).

Thesis (Ph. D.)--University of Texas at Austin, 2005. / Supervisor: Theresa A. Jones. Vita. Includes bibliographical references.

No description available.

Traumatic brain injury (TBI) is the leading cause of disability in individuals under 45 years of age, with mild TBI (mTBI) accounting for the majority of cases. The juvenile brain is in a period of robust synaptic reorganization and myelination, making adolescence a particularly vulnerable time to incur a TBI. Learning and memory deficits that involve the hippocampal formation are often observed following mTBI in adults. To examine this issue in the juvenile brain, we assessed changes in hippocampal synaptic plasticity following closed-head mTBI in male and female Long-Evans rats (25-28 days of age). Synaptic plasticity of field excitatory post-synaptic potentials (fEPSPs) was assessed using in vitro electrophysiology at either one hour, one day, seven days, or 28 days following mTBI in the dentate gyrus (DG) and the cornu ammonis area 1 (CA1) regions of the hippocampus. In female rats, the CA1 region ipsilateral to the impact showed a significant reduction in long-term potentiation (LTP) as early as one hour following mTBI. Similar LTP deficits were apparent at one day in the DG, and persisted to 28 days following injury. In male rats, a deficit in both DG- and CA1-LTP was maximal in the ipsilateral hemisphere by seven days following injury, but these deficits did not persist to 28 days post-injury. These data suggest that the juvenile brain is susceptible to mTBI-induced impairments in plasticity, and sex and regional differences are apparent in the expression and recovery of synaptic plasticity following mTBI. / Graduate

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy