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Genetic dissection of an amygdala microcircuit that gates conditioned fear

2010; Nature Portfolio; Volume: 468; Issue: 7321 Linguagem: Inglês

10.1038/nature09553

1476-4687

Wulf Haubensak, Prabhat S. Kunwar, Haijiang Cai, Stéphane Ciocchi, Nicholas Wall, Ravikumar Ponnusamy, Jonathan Biag, Hong‐Wei Dong, Karl Deisseroth, Edward M. Callaway, Michael S. Fanselow, Andreas Lüthi, David J. Anderson,

Neuroscience and Neuropharmacology Research

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. Here we use molecular genetic approaches to map the functional connectivity of a subpopulation of GABA-containing neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-δ (PKC-δ). Channelrhodopsin-2-assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKC-δ+ neurons inhibit output neurons in the medial central amygdala (CEm), and also make reciprocal inhibitory synapses with PKC-δ− neurons in CEl. Electrical silencing of PKC-δ+ neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus, called CEloff units. This correspondence, together with behavioural data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing. The central amygdala, composed mainly of GABAergic inhibitory neurons, is the part of the brain that processes Pavlovian conditioned fear. Two groups reporting in this issue of Nature use different yet complementary experimental approaches to arrive at similar conclusions about the functional architecture that underlies the conditioned fear response. They find that two microcircuits are involved, one required for fear acquisition and the other for conditioned fear responses. Haubensak et al. use genetically based functional manipulations to identify a subpopulation of GABAergic neurons that has a key role in gating learned fear. Ciocchi et al. use a combination of in vivo electrophysiological, optogenetic and pharmacological approaches in mice to identify three functionally distinct types of neurons that are embedded in a highly organized local disinhibitory network. The central amygdala relies on inhibitory circuitry to encode fear memories, but how this information is acquired and expressed in these connections is unknown. Two new papers use a combination of cutting-edge technologies to reveal two distinct microcircuits within the central amygdala, one required for fear acquisition and the other critical for conditioned fear responses. Understanding this architecture provides a strong link between activity in a specific circuit and particular behavioural consequences.