Genetic dissection of an amygdala microcircuit that gates conditioned fear

By W. Haubensak, Prabhat S. Kunwar, Haijiang Cai, Stéphane Ciocchi, Nicholas R. Wall, R. Ponnusamy, J. Biag, Hong-wei Dong, Karl Deisseroth, Edward M. Callaway and 3 more. Nature, 2010

793 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/b14863a745646a2cf9203de20f6770292bc20db6

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Citations in the corpus

Evoked axonal oxytocin release in the central amygdala attenuates fear response. (2012, positive): “05), possibly as a result of inhibition of local inhibitory circuits in the CeL (Ciocchi et al., 2010; Haubensak et al., 2010).”
What Can Ethobehavioral Studies Tell Us About The Brain’s Fear System? (2016, background): “For example, functional and genetic circuit analyses have shown that the lateral subdivision of the CEA (CEl) is involved in the acquisition of auditory fear conditioning, whereas the medial subdivision of the CEA (CEm) mediates the expression of fear CRs [38,39].”
The Development and Application of Optogenetics (2011, background): “F or p er so na l u se o nl y. expression of conditioned fear (Ciocchi et al. 2010, Haubensak et al. 2010).”
Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling (2011, background): “…halorhodopsin in restricted sets of afferents by vector delivery into upstream brain areas will have to be applied in combination so that control of identified sets of synapses can be achieved (Witten et al., 2010; Stuber, 2010; Wall et al., 2010; Haubensak et al., 2010; Ciocchi et al., 2010).”
RETHINKING THE EMOTIONAL BRAIN (2012, neutral): “…medial CEA (CEm) to the ventrolateral PAG (PAGvl) (Johansen et al., 2011; LeDoux, 2000; Maren, 2001; Fanselow and Poulos, 2005; Davis et al., 1997; Rosenkranz and Grace, 2002; Cousens and Otto, 1998; Paré et al., 2004; Maren and Quirk, 2004; Quirk and Mueller, 2008; Haubensak et al., 2010).”
Whole-brain mapping of direct inputs to midbrain dopamine neurons. (2012, positive): “…the Cre/loxP gene expression system (Gong et al., 2007) with rabies-virus-based transsynaptic retrograde tracing (Wickersham et al., 2007b) to comprehensively identify monosynaptic inputs to a genetically defined neural population (Haubensak et al., 2010; Miyamichi et al., 2011; Wall et al., 2010).”