Anxiety disorder is a common emotional handicap, which seriously affects the normal life of patients and endangers their physical and mental health. The prefrontal cortex is a key brain region which is responsible for anxiety. Action potential and behavioral data of rats in the elevated plus maze (EPM) during anxiety (an innate anxiety paradigm) can be obtained simultaneously by using the in vivo and in conscious animal multi-channel microelectrode array recording technique. Based on maximum likelihood estimation (MLE), the action potential causal network was established, network connectivity strength and global efficiency were calculated, and action potential causal network connectivity pattern of the medial prefrontal cortex was quantitatively characterized. We found that the entries (44.13±6.99) and residence period (439.76±50.43) s of rats in the closed arm of the elevated plus maze were obviously higher than those in the open arm [16.50±3.25, P<0.001; (160.23±48.22) s, P<0.001], respectively. The action potential causal network connectivity strength (0.017 3±0.003 6) and the global efficiency (0.044 2±0.012 8) in the closed arm were both higher than those in the open arm (0.010 4±0.003 2, P<0.01; 0.034 8±0.011 4, P<0.001), respectively. The results suggest that the changes of action potential causal network in the medial prefrontal cortex are related to anxiety state. These data could provide support for the study of the brain network mechanism in prefrontal cortex during anxiety.