Individual Differences in Markers of Cholinergic Signaling Correlating to Fear and Extinction Learning
Date of Award
Open Access Thesis
School of Medicine
David D. Mott
Posttraumatic stress disorder (PTSD) results when individuals are exposed to a life threatening event, assault, serious injury, or other traumatic incident. Individuals with PTSD are impaired in their ability to extinguish fear memories, resulting in intrusive symptoms that impair their ability to live otherwise healthy lives. It remains unclear why some individuals exposed to traumatic events develop PTSD while others do not. Acetylcholine has been shown to play a critical role in fear learning, but its role in fear extinction is not well understood. This study utilized a rat model of fear learning and extinction to determine if individual differences in fear and extinction learning are correlated with markers of cholinergic signaling. This study examined M1 muscarinic acetylcholine receptor (M1 mAChR) and acetylcholinesterase (AChE), both heavily expressed in the basolateral amygdala (BLA), a region that has been heavily implicated in the acquisition, consolidation, and recall of fear and extinction memories. The goal of the present study was to determine if individual differences in these proteins involved in cholinergic signaling in the BLA potentially underlie the individual differences observed in the fear learning and extinction processes. Rats were conditioned using a Pavlovian fear conditioning and extinction paradigm and behavior was analyzed by measuring extent of freezing behavior during each stage of the trial. Grouped differences were found in ability to undergo fear extinction learning and to recall the fear extinction memory. Coronal brain sections were processed for immunofluorescence, labeling for M1 mAChR and AChE, and imaged in order to measure extent of protein expression. Significant correlations were observed between individual’s BLA M1 mAChR densities and ability to undergo fear acquisition and ability to recall fear extinction memories. This lead to the conclusions that M1 mAChR are functioning in the BLA in the processes of fear memory acquisition and extinction memory consolidation and that high expression of M1 mAChR allows for improved ability to undergo fear memory acquisition, resulting in a deficit in fear extinction. No significant correlations were observed between BLA AChE expression and any fear or extinction learning phase. These results add to the growing body of literature implicating M1 mAChR in fear and extinction learning. Therapeutic strategies aimed at altering muscarinic signaling in the amygdala could be implemented in order to enhance fear extinction in animals and patients with PTSD.
Jones, G. C.(2017). Individual Differences in Markers of Cholinergic Signaling Correlating to Fear and Extinction Learning. (Master's thesis). Retrieved from https://scholarcommons.sc.edu/etd/4296