Single Units in the Medial Prefrontal Cortex with Anxiety-Related Firing Patterns Are Preferentially Influenced by Ventral Hippocampal Activity

The medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) functionally interact during innate anxiety tasks. To explore the consequences of this interaction, we examined task-related firing of single units from the mPFC of mice exploring standard and modified versions of the elevated plus maze (EPM), an innate anxiety paradigm. Hippocampal local field potentials (LFPs) were simultaneously monitored. The population of mPFC units distinguished between safe and aversive locations within the maze, regardless of the nature of the anxiogenic stimulus. Strikingly, mPFC units with stronger task-related activity were more strongly coupled to theta-frequency activity in the vHPC LFP. Lastly, task-related activity was inversely correlated with behavioral measures of anxiety. These results clarify the role of the vHPC-mPFC circuit in innate anxiety and underscore how specific inputs may be involved in the generation of behaviorally relevant neural activity within the mPFC. ► mPFC neurons differentiate safe and aversive arms in the EPM, an innate anxiety test ► This differentiation is independent of EPM geometry and the anxiogenic stimulus used ► Units locked to ventral hippocampal theta have stronger EPM task-related firing ► The strength of the mPFC representation varies with behavioral anxiety