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. 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.
Division of Biology 216-76, California Institute of Technology, Pasadena, California 91125, USA.
Wulf
W
Haubensak
Prabhat S
PS
Kunwar
Haijiang
H
Cai
Stephane
S
Ciocchi
Nicholas R
NR
Wall
Ravikumar
R
Ponnusamy
Jonathan
J
Biag
Hong-Wei
HW
Dong
Karl
K
Deisseroth
Edward M
EM
Callaway
Michael S
MS
Fanselow
Andreas
A
Lüthi
David J
DJ
Anderson
D000679:Amygdala / Q000033:anatomy & histology / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D000818:Animals; D001370:Axonal Transport; D002478:Cells, Cultured; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D046352:Freezing Reaction, Cataleptic; D005821:Genetic Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005680:gamma-Aminobutyric Acid; D051745:Protein Kinase C-delta