Schutsky, Keith B
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PublicationThe Role of Stress, Glucocorticoids & β-Adrenergic Signaling in Aversive, Hippocampus-Dependent Memory Retrieval(2011-05-16) Schutsky, Keith BStudies in wild-type rats and mice, and mutant mice lacking norepinephrine (NE) demonstrate that NE, β1-adrenergic, cAMP/PKA and Epac signaling are required for intermediate-term hippocampus-dependent memory retrieval. Although it has been proposed that glucocorticoids (GCs) facilitate β-adrenergic signaling to impair retrieval, neither a specific requirement for NE nor a definitive mechanism as to how this interaction occurs has been established. This thesis provides compelling evidence that 1) GCs do not require (but can synergize with) the adrenergic system to impair hippocampus-dependent memory retrieval; 2) GCs and xamoterol interact with the β2 receptor to impair retrieval; 3) β2 receptors signal through Gi/o in the hippocampus to impair retrieval, acting to negate the facilitation of hippocampus-dependent memory retrieval mediated by β1-Gs signaling; 4) GCs impair retrieval through possibly direct interaction with the β2 receptor; 5) β2 signaling is required for retrieval and may be required for short-term maintenance of fear memory; 6) β3 signaling influences retrieval; 7) interactions between β receptors are important and net effects of β receptor stimulation (or antagonism) on hippocampal cAMP signaling likely determine the degree of retrieval impairment expressed, as individual β receptors can have similar or opposing effects on cAMP levels; and 8) adrenergic and glucocorticoid influences on retrieval are limited by the age of the memory.