Genetic dissection of an amygdala microcircuit that gates conditioned fear

The role of different amygdala nuclei (neuroanatomical subdivisions) in processing Pavlovian conditioned fear has been studied extensively, but the function of the heterogeneous neuronal subtypes within these nuclei remains poorly understood. We used molecular genetic approaches to map the functional connectivity of a subpopulation of GABAergic neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-delta (PKCδ). Channelrhodopsin-2 assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKCδ(+) neurons inhibit output neurons in the medial CE (CEm), and also make reciprocal inhibitory synapses with PKCδ(−) neurons in CEl. Electrical silencing of PKCδ(+) neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus (CS), called CEl(off) units (Ciocchi et al, this issue). This correspondence, together with behavioral data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing.