, 2008 and Quirk et al., 2003). Although considerable evidence indicates that an IL-ITC circuit maintains extinguished fear, there are both behavioral and neural data that are not readily explained by this model. First, an IL-mediated inhibition of CE (which presumably operates to suppress fear output nonspecifically) by an extinguished CS should block fear to another unextinguished CS when the two stimuli are presented together, but evidence for this is scant (Leung and Westbrook, 2008). Moreover, an IL-mediated suppression of fear by inhibitory ITC cells

overlooks the observation that neurons upstream in the basal and lateral amygdala themselves show decrements in activity after extinction (Herry et al., 2008 and Repa et al., 2001) that readily renew outside of the extinction context (Hobin et al., 2003). These observations suggest that local inhibition within the BA may selectively Selleckchem MEK inhibitor (and reversibly) silence neurons in the BA after extinction to suppress fear. In an article in the current issue of Neuron, Trouche et al. (2013) examined this possibility by

labeling neurons in the BA involved in contextual fear conditioning and then examining whether those neurons are reactivated during memory retrieval after extinction. To this end, Tariquidar research buy they used a TetTag reporter mouse that expresses GFP under the control of a c-fos promoter when doxycycline is removed from the diet ( Reijmers et al., 2007). After labeling neurons during fear Edoxaban conditioning, Trouche et al. (2013) then assessed ex vivo GFP and Zif expression after a retrieval test to determine whether neurons active during fear conditioning remained active after extinction. Interestingly, they found that roughly 15% of the BA neurons tagged during fear conditioning were reactivated in nonextinguished

mice. However, only half that number of neurons was reactivated in animals that underwent an extinction procedure. In other words, extinction training silenced a large proportion of BA neurons that had been active during fear conditioning. They did not observe extinction-induced silencing in either hippocampal area CA1 or IL, suggesting that the silencing was rather specific to the BA. Hence, these results imply that the extinction of fear drives local inhibitory interneurons to establish synaptic contacts with a subset of excitatory BA neurons recruited during fear conditioning. To further explore this possibility, Trouche et al. (2013) examined the colocalization of proteins unique to inhibitory interneurons in active and silenced BA neurons. Interestingly, they found that silenced neurons exhibited significantly greater perisomatic GAD67 labeling, suggesting a proliferation of inhibitory GABAergic synapses on these neurons. In line with this idea, they found that the density of perisomatic parvalbumin (PV) staining was greater in silenced neurons and these changes were only observed in animals undergoing extinction.