Huntington’s disease (HD) is a devastating neurological condition with a spectrum of cognitive, psychiatric, and motor symptoms. Because of substantial cell death seen in post mortem tissue the striatum has largely been the focus of many HD studies. Accumulating evidence also suggests significant structural and functional changes in cerebral cortex, including prefrontal cortex (PFC), in HD patients. I have previously shown that neuronal firing patterns recorded in vivo, such as burst activity and synchrony, are altered in PFC of the R6/2 mouse model of HD. The goal of my dissertation research is to characterize the extent of PFC dysfunction in the R6/2 mouse by using physiological, anatomical, behavioral, and pharmacological techniques. First, both electrophysiological recordings and neuronal reconstructions were obtained from each mouse. I found that R6/2 mice had significantly retracted basilar dendrites and this retraction was related to impairments in bursting and synchrony. Next, mice were trained in fear conditioning and extinction, a behavioral paradigm that is PFC dependent. I found that R6/2 mice extinguish conditioned fear faster than wild-types (WT) and that PFC neurons recorded during training have less extinction related activation, which may account for faster extinction. In the final aim, I sought to determine if metabotropic glutamate receptors (mGlur) 2/3 were a viable target for prefrontal dysfunction with two experiments. In the first experiment, PFC activity was recorded and the response to an acute injection of an mGlur2/3 agonist was measured. Mice in the second experiment were treated with an mGlur2/3 agonist for 14 days and PFC activity was recorded. In both experiments, activation of mGlur2/3 did not attenuate abnormal firing patterns in PFC of R6/2 mice. Overall, these experiments demonstrate that PFC disruptions in the R6/2 mouse are a circuit level phenomenon that closely models the human HD condition. These results also further our understanding of the pharmacology underlying PFC dysfunction and potential therapeutic targets.