Genetic dissection of an amygdala microcircuit that gates conditioned fear

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

Research output: Contribution to journalArticlepeer-review

545 Scopus citations

Abstract

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 CEl off units. This correspondence, together with behavioural data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing.

Original languageEnglish (US)
Pages (from-to)270-276
Number of pages7
JournalNature
Volume468
Issue number7321
DOIs
StatePublished - Nov 11 2010
Externally publishedYes

ASJC Scopus subject areas

  • General

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