Fibroblast growth factor-2: a novel enhancer of memory

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Copyright: Graham, Bronwyn Margaret
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Abstract
This thesis investigated the role of Fibroblast Growth Factor-2 (FGF2), a potent neurotrophic factor that is involved in brain development, on the formation of long-term memory in developing rats. The first series of experiments examined the effects of early-life exposure to systemically administered FGF2 on learning that occurred later in life (Chapter 2). While a single injection of FGF2 on post natal day (PND) 1 did not lead to any detectable changes in contextual fear later in life, five days of FGF2 exposure (on PNDs 1-5) led to enhanced long-term memory for contextual fear in rats trained at PND 16 and 23. Furthermore, repeated early-life FGF2 allowed PND 16 rats to use contextual information in more complex ways, leading to precocious context-dependent extinction of conditioned fear. The second series of experiments examined the effects of acute systemic FGF2, administered at the time of training, on long-term memory (Chapter 3). FGF2 enhanced contextual and cued fear conditioning when administered prior to or immediately after training in rats of a variety of ages. The observed facilitation in fear was not due to FGF2 increasing sensitivity to footshock. The third and fourth series of experiments examined the effects of acute FGF2 on extinction of conditioned fear in PND 23 rats. FGF2 enhanced extinction when administered before or immediately (but not four hours) after extinction, and only when observable within-session extinction occurred (Chapter 4). FGF2-treated rats also showed reduced susceptibility to reinstatement and renewal, two common forms of relapse, and FGF2-treated rats also showed NMDA-dependent re-extinction, suggesting that FGF2 may fundamentally change the quality of extinction (Chapter 5). These experiments are the first to implicate exogenous FGF2 in the formation of long-term memory. The theoretical and clinical implications of these findings are discussed in light of current models of the development of memory and models of fear extinction.
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Author(s)
Graham, Bronwyn Margaret
Supervisor(s)
Richardson, Rick
McNally, Gavan
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Publication Year
2010
Resource Type
Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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