Interestingly, Trouche et al. (2013) also observed a subset of neurons that were not silenced after extinction, and these cells exhibited higher densities of perisomatic cannabinoid receptor 1 (CB1R) labeling. Because CB1Rs limit GABA release, these receptors suggest a mechanism for sustained activity in neurons that were not silenced by the extinction procedure. this website Altogether, the data reveal that extinction learning remodels inhibitory synaptic input onto BA neurons to limit the expression of fear. The reorganization of inhibitory synaptic input onto the specific network of neurons encoding the

fear memory is a novel, selective, and direct mechanism for limiting conditioned fear responses after extinction. Although the cellular

mechanisms underlying these synaptic changes are not yet understood, a large number of studies suggest that NMDA receptors may be involved (Falls et al., 1992 and Zimmerman and Maren, 2010). How NMDA receptors mediate both long-term potentiation of excitatory synapses onto BA neurons encoding fear conditioning and the remodeling of perisomatic inhibition onto these neurons after extinction is a fascinating question. Whatever the mechanism, these data are consistent with the idea that extinction involves new learning that suppresses learned fear responses, rather than erasing the fear memory itself. Of course, a critically important question concerns how these and GBA3 other inhibitory mechanisms are themselves silenced during fear relapse. That is, GSK1210151A manufacturer how does fear in response to an extinguished CS renew, for example, when the CS is presented outside the extinction context? One possibility is that the activity of inhibitory interneurons in the BA is context dependent; the activity of these neurons may be elevated in the extinction context but dampened in a dangerous context. Another possibility is that fear relapse is mediated by BA neurons that remain active after extinction. Clearly, further work is

required to understand how target-specific silencing of BA neurons is modulated to allow for the context-dependent expression of fear. It is becoming clear that hippocampal and medial prefrontal cortical projections to basal and lateral amygdala neurons are involved in fear relapse after extinction (Herry et al., 2008, Knapska et al., 2012 and Orsini et al., 2011). Whether these circuits ultimately suppress inhibitory activity in the amygdala or drive activity in BA neurons during fear relapse (or both) remains to be examined. Clearly, the use of activity-dependent neuronal tags to track neuronal populations engaged during encoding and retrieval processes is a promising strategy to answer these questions.