Units with more

robust paradigm-related activity were more strongly modulated by vHPC theta-frequency activity, indicating their participation in a functional network involving both structures. Lastly, and somewhat counterintuitively, animals with higher avoidance of the aversive open arms check details of the EPM had fewer mPFC units with paradigm-related activity, as well as overall higher firing rates compared to mice that displayed lower avoidance. These results underscore how specific inputs may be involved in the generation of behaviorally relevant neural activity within the mPFC and refine our understanding of the role of the vHPC-mPFC circuit in EPM behavior. To characterize the activity

of mPFC single units in the EPM, 79 well-isolated cortical single units were recorded from the deep layers of the prelimbic cortex in 17 129/SvevTac mice during exploration of a standard cross-shaped EPM under dim (200 lux) illumination. The mean firing rate of these units was 2.05 ± 0.64 Hz. Units with fewer than 100 spikes (n = 10) were excluded from further analysis. Spatial firing maps revealed that many of the single units tended to fire in specific subcompartments of the EPM (Figures 1A–1C). For example, the unit shown in Figure 1A fired preferentially in the two closed, or “safe” arms, while the unit in Figure 1B fired preferentially in the two open, or “aversive” arms. To further characterize firing patterns across the entire population of recorded mPFC units, normalized firing rates (% difference from

BMS-754807 in vitro mean firing rate) were calculated in the five compartments (each open arm; each closed arm; and the center) of the EPM (Figures 2B and 2C). Units with task-related firing Bay 11-7085 patterns would be expected to have similar firing rates in arms of the same type (open/aversive versus closed/safe), and negatively correlated firing rates in arms of opposite type. In line with this prediction, firing rates in both closed arms (r = +0.38, p < 0.0001, Figure 2D) and both open arms (r = +0.25, p < 0.04, Figure 2E) were positively correlated, while firing rates across arms of different types were inversely correlated (r = −0.64 p < 0.0001, Figure 2F). Note that with the presence of a center compartment, the inverse correlation between arms of different types is not an automatic consequence of the normalization technique (Figure S1, available online). Negative correlations between one open and one closed arm were present after only 90 s of exploration of the EPM (r = −0.47, p < 0.001), demonstrating that single unit representations of EPM arms arise quickly and do not require extensive exploration of the maze. The results were not due to novelty, as similar results were found during a second exposure to the EPM 24 hr later (Figures 3A and 3B).