Journal Article

Encoding of conditioned fear in central amygdala inhibitory circuits

Ciocchi, Stephane, Vlachos, Ioannis, Lüthi, Andreas, Müller, Christian, Ehrlich, Ingrid, Sprengel, Rolf, Deisseroth, Karl, Wolff, Steffen B. E., Stadler, Michael B., Herry, Cyril, Letzkus, Johannes J., Grenier, François

2010

Overview

The central amygdala (CEA), a nucleus predominantly composed of GABAergic inhibitory neurons, is essential for fear conditioning. How the acquisition and expression of conditioned fear are encoded within CEA inhibitory circuits is not understood. Using in vivo electrophysiological, optogenetic and pharmacological approaches in mice, we show that neuronal activity in the lateral subdivision of the central amygdala (CEl) is required for fear acquisition, whereas conditioned fear responses are driven by output neurons in the medial subdivision (CEm). Functional circuit analysis revealed that inhibitory CEA microcircuits are highly organized and that cell-type-specific plasticity of phasic and tonic activity in the CEl to CEm pathway may gate fear expression and regulate fear generalization. Our results define the functional architecture of CEA microcircuits and their role in the acquisition and regulation of conditioned fear behaviour. The neural circuitry of fear 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/114/116/2395 / 631/378/1457/1284 / 631/378/1595/2636 / 631/601/18 / Action Potentials / Amygdala - anatomy & histology / Amygdala - cytology / Amygdala - physiology / Analysis / Animals / Behavior / Behavioral psychophysiology / Biological and medical sciences / Conditioning, Classical - physiology / Fear - physiology / Freezing Reaction, Cataleptic / Fundamental and applied biological sciences. Psychology / GABA / gamma-Aminobutyric Acid - metabolism / Genetic code / Health aspects / Humanities and Social Sciences / Male / Mice / Mice, Inbred C57BL / multidisciplinary / Neural Inhibition - physiology / Neural Pathways - cytology / Neural Pathways - physiology / Neurology / Neuronal Plasticity - physiology / Neurons / Neurons - physiology / Neurotransmission and behavior / Physiological aspects / Psychology. Psychoanalysis. Psychiatry / Psychology. Psychophysiology / Science / Science (multidisciplinary)