Neural activity within the brain underlies complex behavior that allows us to interact with our environment. The anterior cingulate cortex (ACC) is believed to mediate appropriate behavioral responses by integrating emotional and cognitive information about external stimuli. If this understanding is correct, then neural activity within the ACC must therefore correlate with behavioral output in response to external experience. The aim of this thesis is to bridge mechanisms identified in vitro with behaviors observed in vivo to determine the neural substrates of ACC mediated behavior. This thesis focuses on glutamatergic receptors that have been established as mediators of excitatory transmission in the ACC. Through a combination of behavioral, pharmacological, biochemical, and electrophysiological methods, this thesis examined how behaviors observed in mouse models of fear learning, chronic pain, and itch correspond with in vitro observations of ACC neuronal activity. Three sets of experiments are presented. The first set investigated cortical LTP-like mechanisms, and assessed whether they could mediate fear learning. These sets of experiments provide in vivo evidence that trace fear learning requires rapid, NMDA receptor dependent, cortical AMPA receptor insertion. The second set of experiments investigated the contribution of forebrain CREB-mediated transcription in behavioral manifestations of chronic pain. These experiments show that forebrain overexpression of CREB is sufficient to enhance mechanical allodynia in animal models of chronic inflammatory or neuropathic pain. Lastly, the final set of experiments show that pruritogen-induced scratching corresponds with enhanced excitatory transmission in the ACC through KA receptor modulation of inhibitory circuitry. Through investigations of multiple behaviors linked to ACC activity, this thesis presents evidence that manifestations of behavior can be observed at the molecular level, and indicates that molecular mechanisms involved in ACC synaptic activity are a good target for translational research into pathological conditions that are related to abnormal ACC activity.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/65655 |
| Date | 18 July 2014 |
| Creators | Descalzi, Giannina |
| Contributors | Zhuo, Min |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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