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Abstract
The experiments reported in this thesis investigated the effects of dorsomedial prefrontal cortex (dmPFC) chemogenetic excitation on fear learning. The first series of experiments validated the Designer Receptor Exclusively Activated by Designer Drug approach in manipulating dmPFC neuronal activation. Experiments 1A and 1B demonstrated that hM3Dq expression coupled with CNO application increased dmPFC excitation; and, that hM3Dq expression could be restricted to glutamatergic neurons. The next series of experiments investigated the effects of dmPFC chemogenetic excitation on learning in response to positive fear prediction error. Experiments 2, 3 and 4A demonstrated that chemogenetic excitation of dmPFC glutamatergic neurons prevented the associative blocking of learned fear so that a CS was learned about even in the absence of prediction error. However, chemogenetic excitation did not affect the acquisition of simple Pavlovian fear. The last series of experiments investigated the effects of chemogenetic excitation of dmPFC neurons on negative fear prediction error. Experiments 4B, 5 and 6 found that chemogenetic excitation of dmPFC neurons did not disrupt extinction or overexpectation of fear and thus had no influence on learning in response to negative prediction error, regardless of US presence. These results were interpreted to mean that rather than simply being a passive relay of a prediction error signal generated elsewhere in the brain, dmPFC chemogenetic excitation acts to maintain the associability of novel or ambiguous cues. This effect of dmPFC chemogenetic excitation is better aligned with CS rather than US processing models of fear prediction error and also better aligned with the top-down or higher order functions typically ascribed to the PFC.