Extinction had no significant effect on the activation of BA neurons that were

not tagged during fear conditioning (GFP−Zif+, Figure 1H). We analyzed the BA fear memory circuit by defining two types of fear neurons (i.e., tagged during fear conditioning): silent fear neurons (GFP+Zif−, fear neurons not reactivated during retrieval) and active fear neurons (GFP+Zif+, fear neurons reactivated during retrieval) ( Figure 1I). We found that fear extinction caused a 2.3-fold decrease in the number of active BA fear neurons, with a subgroup of fear neurons remaining active after extinction (GFP+Zif+; Figures 1J and S1D). This extinction-induced silencing of the BA fear memory circuit, caused by contextual fear extinction, is similar to that previously RG 7204 found in electrophysiological studies on tone fear extinction ( Amano et al., 2011, Herry et al., 2008 and Livneh and Paz, 2012). In addition, the observed concomitant reduction in active BA fear neurons and freezing replicates previous studies ( Herry et al., 2008 and Reijmers et al., 2007) and reflects the causative role of the basal amygdala in the behavioral expression of contextual fear ( Maren, 1998). Therefore, our results provide further support for a model in which extinction decreases Y-27632 concentration fear by silencing the fear memory circuit within the BA. We next explored where

extinction acted to cause a silencing of the BA fear memory circuit. We first addressed the possibility that contextual fear extinction might act on brain regions upstream of the BA and thereby indirectly silence fear

neurons in the BA. The BA receives inputs from the CA1 area of the hippocampus and from the infralimbic prefrontal cortex, brain regions that have been implicated in fear extinction (Hartley and Phelps, 2010 and Orsini and Maren, 2012). We therefore tested whether fear extinction altered the activation of excitatory neurons in the CA1 region of the hippocampus (both dorsal and ventral: dCA1 and vCA1) and in the infralimbic prefrontal cortex (IL). We analyzed the same brains that were used for the BA analysis, since the TetTag mouse enables the tagging of neurons recruited by fear conditioning throughout secondly the whole brain (Deng et al., 2013, Garner et al., 2012, Liu et al., 2012, Matsuo et al., 2008, Reijmers et al., 2007, Tayler et al., 2011 and Tayler et al., 2013). As expected, the FC and FC+EXT groups had similar percentages of neurons tagged in these brain regions during contextual fear conditioning (Figures 2A and 2B). Contextual fear extinction did not alter the activation of nontagged dCA1 and vCA1 neurons during retrieval (Figure 2C) or the reactivation of tagged dCA1 and vCA1 neurons during retrieval (Figures 2B and 2D). These results are consistent with a previous study reporting that contextual fear extinction acts on a population of CA1 neurons that is segregated from the CA1 neurons recruited during fear conditioning (Tronson et al.