Mechanisms Underlying the Impact of Novelty Exposure on Arousal and Memory Improvement: Involvement of Noradrenergic Transmission within the Amygdala and Hippocampus

Multiple lines of research indicate that inclusion of novel experiences prior to or following learning affects neural processes that form and store new events into memory storage. Discovery of this phenomenon has inspired a new era of research to understand how novelty impacts cognitive processing at multiple levels of analysis. Findings from these studies reveal exposure to an unfamiliar environment or the presentation of novel stimuli increases physiological arousal, firing frequencies within specific ensembles of neurons and induces a myriad of intracellular changes that increase synaptic plasticity associated with new learning. Volumes of knowledge have emerged from these efforts although few studies have addressed which neurotransmitter systems are responsible for initiating novelty induced changes in brain structures that encode, process and store new events into long term memory. An additional shortcoming of the literature concerns the disproportionate number of studies that focus primarily on understanding how novelty exposure influences dorsal hippocampal functioning despite accumulating evidence that neuronal activity in the amygdala and ventral hippocampus may also be affected by novelty.

Studies examining the mechanisms that lead to better memories for emotionally arousing events reveal heightened states of physiological arousal potentiate norepinephrine output within key limbic structures that encode and store new events into memory. This effect is mediated in part by the influence arousal exerts on the firing rates of norepinephrine containing neurons in the locus coeruleus (LC). LC neurons are excited when an organism is placed in a new context and subsequent actions of norepinephrine on its respective target structures, such as the hippocampus and amygdala, produces a number of intracellular changes associated with synaptic plasticity. Chapter 2 and 3 of this dissertation will examine whether exposure to a novel context impacts norepinephrine release in the basolateral amygdala and ventral hippocampus. Additionally, experiments in these chapters will determine if beta-noradrenergic receptor activity in the basolateral and central nuclei of the amygdala as well as the ventral hippocampus mediates the beneficial effects of novelty on memory formation. Lastly, chapter 3 will also determine if activation of AMPA receptors in the ventral hippocampus is critical for novelty-dependent memory enhancement. This study will tie both findings that glutamate is increased in this area following novel events and glutamatergic projections from basolateral neurons innervate ventral hippocampus neurons activated by novelty to memory processes. Collectively, the data obtained from these dissertation experiments will further our understanding for how novelty impacts the brain to enhance memory.