Memory modulation by emotional arousal: Convergent evidence on the contribution of ascending vagal fibers on central noradrenergic systems involved in consolidation

The secretion of epinephrine in response to meaningful or emotionally laden events plays an integral role in modulating brain systems that consolidate new experiences into long term memory. The impermeability of the blood brain barrier to epinephrine represents an important obstacle in understanding how this peripheral arousal related hormone initiates neurochemical changes that lead to effective memory formation. This obstacle necessitated the identity of a putative pathway capable of conveying physiological changes produced by epinephrine to limbic structures that incorporate arousal and affect related information into memory. A major theme of the proposed studies is that peripheral vagal fibers may represent such a mechanism. Thus, studies developed for the dissertation were all developed to test separate aspects of this hypothesis.; The dissertation is organized into six main chapters that begin with a discussion of literature providing a background and the rationale for conducting the proposed studies. Chapter 2 demonstrates a contribution of ascending vagal fibers in modulating memory for responses learned under behavioral conditions that produce emotional arousal by manipulating appetitive stimuli as opposed to administering noxious stimuli such as footshock. The experiment in Chapter 3 identified changes in neuronal activity induced by epinephrine injection or vagus nerve stimulation in key limbic areas and lower brain noradrenergic nuclei using Fos and Fos/DBH (dopamine-beta-hydroxylase) immunocytochemistry. The similar patterns of Fos expression induced by either epinephrine injection or vagal stimulation suggest that increased adrenergic and visceral activity in the periphery is transmitted via the vagus to influence central noradrenergic systems that affect the modulation of memory.; Chapter 4 reports how norepinephrine output in both the nucleus accumbens and basolateral amygdala is influences by electrical stimulation of the vagus nerve at an intensity that was shown to improve memory in Chapter 2. The consequences of elevating peripheral concentrations of epinephrine on both vagal nerve discharge and norepinephrine release in the amygdala was assessed simultaneously in Chapter 5. A combination of electrophysiological recording of vagal afferent fibers and in vivo microdialysis in basolateral amygdala was employed. Collectively, findings emerging from this dissertation establish the importance of ascending fibers of the vagus nerve as an essential pathway for conveying the peripheral consequences of physiological arousal on brain systems that encode new information into memory storage. The implications and significance of the present experiments are discussed in Chapter 6.