Extinction learning: neurological features, therapeutic applications and the effect of aging

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Extinction learning consists of the usually gradual inhibition of the retrieval of a previously learned response or behavior. It is widely used for the treatment of syndromes of learned fear, such as phobias and post-traumatic stress disorder. It relies on well-identified molecular processes in the hippocampus, basolateral amygdala, ventromedial prefrontal cortex (vmPFC) and entorhinal cortex. In humans, thickness of the orbital cortex, vmPFC and the anterior cingulate cortex correlates with the capacity to extinguish. The three regions are functionally inter-related (see below). The development of learned fear syndromes in humans is viewed by many as being due to a deficit of extinction, and so of the capacity to deal with fear. Blockade of NMDA receptors, inhibition of protein synthesis in the vmPFC or blockade of protein synthesis or of various molecular signaling cascades in the hippocampus, amygdala or entorhinal cortex impairs extinction. d-cycloserine, a partial agonist at NMDA receptors, enhances extinction in animals and humans and may help extinction to exert its therapeutic effect. Cannabinoids also enhance extinction, acting through CB1 receptors, but their therapeutic use is not warranted.