The Effect of Lateral Periaqueductal Grey on Non-Associative and Associative Learning Processes
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The Effect of Lateral Periaqueductal Grey on Non-Associative and Associative Learning Processes

Abstract

The present thesis investigated neural correlates of Stress Enhanced Fear Learning (SEFL) in the periaqueductal grey (PAG). In the first set of experiments, we found that SEFL is transmodal. Animals that have received a stressful experience in the form of foot shock, they will demonstrate enhanced fear conditioning in the future to a white noise. Further, we found that white noise is not significantly stressful enough to cause SEFL. We demonstrated that footshock causes activity burst, a “circa-strike” behavior, as well as “post-encounter” freezing. In contrast, white noise at most caused freezing. This allowed us to use noise as a stress control when examining neural correlates of SEFL in order to verify that activity was not elicited by any fear or freezing per se. In our next set experiments, we investigated neural correlates of SEFL in PAG subregions using the activity marker cFos. We compared activity resulting from either shock stress or noise stress. In central positions of PAG, the lateral periaqueductal gray (lPAG) and ventral-lateral PAG (vlPAG) both showed a graded response to stress, such that there was the greatest amount of cFos to shock stress, then noise stress, and finally low levels in homecage controls. We also saw this pattern in caudal vlPAG. However, in caudal lPAG, only shock stress caused significantly more expression than homecage controls, suggesting it is specifically severe stress that recruits the causal lPAG. Therefore, caudal lPAG may uniquely contribute to the ability of stress to cause SEFL. In our final set of experiments, we tested the necessity of lPAG for SEFL using optogenetics. lPAG was inhibited during each shock presentation that occurs during shock stress. Surprisingly, we found that lPAG was not necessary for SEFL. Next, we asked whether lPAG might be important instead for the associative components of fear. To test this, we optogenetically inhibited lPAG during the shock in a Pavlovian fear conditioning procedure. Inhibiting lPAG during each shock presentation caused enhanced fear to both the shock-paired tone and context. Taken together, our work suggests that lPAG signals predictive teaching information about the shock during associative learning.

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