05, Wilcoxon’s test), Galunisertib chemical structure consistent with the notion that information from the vHPC plays a role in generating anxiety-related firing patterns. As expected, there was no difference in EPM scores comparing units that followed dHPC

to those that did not (Figure 9E). mPFC single units appear to differentiate between safe and aversive locations in the EPM. However, it is unclear whether this feature of mPFC activity is related to behavioral measures of anxiety in the EPM. In order to investigate this hypothesis, the mean EPM score for each animal was calculated for all mice with at least three simultaneously recorded single units in the EPM. Mean EPM scores per animal were significantly positively correlated with open arm exploration (r = +0.65, Figure 10A). Thus, in animals that display behavioral avoidance of the

open arms (dark gray points in Figure 10A), mPFC single units show less differentiation between open and closed arms. To strengthen this association of EPM scores with anxiety-like behavior, we calculated EPM scores in serotonin 1A receptor knockout (5-HT1AR KO) mice. 5-HT1AR KO mice have a robust phenotype of increased anxiety, as well as increased http://www.selleckchem.com/products/Everolimus(RAD001).html strength of vHPC and mPFC theta oscillations, when exposed to the EPM (Gross et al., 2002, Klemenhagen et al., 2006, Ramboz et al., 1998 and Adhikari et al., 2010b). In agreement with the unexpected result that lower EPM Oxalosuccinic acid scores are associated with higher avoidance, 5-HT1AR KO mice had lower EPM scores than WT mice (Figures 10B and 10C). Indeed, the distributions of EPM scores of avoidant WT mice (those that spent < 50% time in the open arms) and 5-HT1AR KO mice were not significantly different from the chance distribution of EPM scores generated after randomly shuffling spike

location (Wilcoxon’s test, p < 0.79), suggesting that these mice fail to form appropriate representations of the EPM in the mPFC. This result is consistent with the notion that the failure to represent the EPM is related to anxiety. Why would mice that avoid the aversive arms fail to develop mPFC representations of aversiveness? One clue comes from overall firing rates. Mean absolute firing rates in the EPM tended to be higher in avoidant WT and 5-HT1AR KO mice compared to WT mice that failed to avoid the open arms (mean ± SEM firing rate = 2.8 ± 0.58 and 2.94 ± 0.80 Hz for avoidant WT and 5-HT1AR KO mice, respectively, compared to 1.57 ± 0.3 Hz for nonavoidant WT mice). There were no significant differences in the firing rates between these groups in recordings obtained in a control, nonanxiogenic familiar environment. Thus, the elevated firing rates in the EPM of avoidant mice are a consequence of greater increases in rate relative to the familiar environment (Figure 10D). These increases are significant only in avoidant WT and 5-HT1AR KO mice (Wilcoxon’s test, p < 0.05).