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 and David J. Anderson ()
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Wulf Haubensak: California Institute of Technology
Prabhat S. Kunwar: California Institute of Technology
Haijiang Cai: California Institute of Technology
Stephane Ciocchi: Friedrich Miescher Institute for Biomedical Research
Nicholas R. Wall: Systems Neurobiology Laboratory, The Salk Institute for Biological Studies
Ravikumar Ponnusamy: University of California, Los Angeles, Los Angeles, California 90095, USA
Jonathan Biag: Laboratory for Neuroimaging, University of California, Los Angeles, Los Angeles, California 90095, USA
Hong-Wei Dong: Laboratory for Neuroimaging, University of California, Los Angeles, Los Angeles, California 90095, USA
Karl Deisseroth: Stanford University
Edward M. Callaway: Systems Neurobiology Laboratory, The Salk Institute for Biological Studies
Michael S. Fanselow: University of California, Los Angeles, Los Angeles, California 90095, USA
Andreas Lüthi: Friedrich Miescher Institute for Biomedical Research
David J. Anderson: California Institute of Technology

Nature, 2010, vol. 468, issue 7321, 270-276

Abstract: 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 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.

Date: 2010
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DOI: 10.1038/nature09553

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