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Trends Neurosci. 2012 Mar;35(3):145-55. doi: 10.1016/j.tins.2011.10.003. Epub 2011 Nov 25.

Fear conditioning and extinction: emotional states encoded by distinct signaling pathways.

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Department of Psychiatry and Behavioral Sciences, The Asher Center for Study and Treatment of Depressive Disorders, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.


Conditioning and extinction of fear have traditionally been viewed as two independent learning processes for encoding representations of contexts or cues (conditioned stimuli, CS), aversive events (unconditioned stimuli, US), and their relationship. Based on the analysis of protein kinase signaling patterns in neurons of the fear circuit, we propose that fear and extinction are best conceptualized as emotional states triggered by a single CS representation with two opposing values: aversive and non-aversive. These values are conferred by the presence or absence of the US and encoded by distinct sets of kinase signaling pathways and their downstream targets. Modulating specific protein kinases thus has the potential to modify emotional states, and hence, may emerge as a promising treatment for anxiety disorders.

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