Figure 3. Contextual modulation of fear after extinction.

After extinction, rats suppress their fear to the conditioned stimulus (CS) within the extinction context, but exhibit high levels of fear to the CS in other contexts. The renewal of fear and the recall of extinction are regulated by hippocampal-prefrontal control of the amygdala. As illustrated in the left panel, during renewal, the hippocampus (HPC) transmits contextual information to the basal amygdala (BA) via a direct projection, as well as through indirect projections via the prelimbic cortex (PL) of the prefrontal cortex (Orsini et al., 2011). These projections may synapse upon “fear” neurons within the BA, which selectively fire to a CS during fear conditioning and renewal (Herry et al., 2008). ”Fear” neurons in the BA may send excitatory projections directly to the centromedial amygdala (CeM) to drive the expression of fear (Tye et al., 2011). CeM excitation might also be mediated by dampening GABergic inhibition from intercalated cells (ITC) and CeL inputs to CEm (Royer et al., 1999; Tye et al., 2011). During extinction (right panel), the infralimbic cortex (IL) of the prefrontal cortex inhibits CEm output by driving inhibitory ITC neurons (Quirk et al., 2003; Berretta et al., 2005). IL inputs might also synapse on “extinction” neurons within the BA, which have been shown to fire selectively to an extinguished CS (Herry et al., 2008). “Extinction” neurons might then influence activity within the CeA through several routes, possibly by driving inhibitory ITC or CeL neurons that limit CeM activity. BA-CeL pathway is anxiolytic and this decrease in anxiety is mediated by the inhibition of the CeM (Tye et al., 2011). Although the hippocampus is not necessary for the expression of extinction, its projections to both IL and BA may be involved in extinction under some conditions.