Tuesday, August 12, 2008

Circuits that switch fear ON and OFF

Sah and Westbrook write a brief review of work by Herry et al. and Likhtik et al. Here are some mixed and edited clips:
The work pinpoints the neural circuits that mediate the bidirectional transition between a defensive behaviour — fear — and the default exploratory behaviour. These functions are evolutionarily old, and their dysfunction is thought to underlie a host of anxiety disorders in humans, including post-traumatic stress and panic disorder

To study the neural mechanisms that mediate fear responses, fear conditioning is widely used. In a typical procedure, animals are exposed to a normally harmless stimulus (such as a sound or light) before a brief exposure to an aversive stimulus — typically a foot shock. A few such rounds of pairing the harmless (conditioned) stimulus with the aversive (unconditioned) stimulus create an association between them in the animals' minds...It is important to study how fear is first learned. However, the pertinent question for clinicians is how fear can be eliminated or reduced. Extinction of fear occurs when the association between the conditioned and the unconditioned stimuli is broken by repeated presentations of the conditioned stimulus only. But does the association get completely erased from the memory? The answer is no. Although the conditioned stimulus eventually fails to elicit fear responses, much, if not all, of the original learned fear survives extinction. So when the extinguished conditioned stimulus is tested either during, or shortly after, exposure to a dangerous context again, the conditioned fear is renewed spontaneously. Extinction therefore involves new learning, and its activation by situational cues inhibits the expression of fear responses to the conditioned stimulus.

During fear conditioning, convergence of inputs from the conditioned stimulus (CS) and unconditioned stimulus (US) to fear neurons in the basolateral amygdala (BLA) leads to potentiation of the conditioned input and activation by the CS of neurons in the central nucleus (CEA) that initiates physiological and behavioural responses characteristic of fear. b, During extinction, inputs from the medial prefrontal cortex (PFC) activate neurons in the intercalated cell masses (ICMs) — either directly or through activation of extinction neurons in the basolateral amygdala — which then inhibit the activity of fear output neurons in the CEA. c, During fear renewal, inputs from the hippocampus, which evaluates the current context, activate inhibitory interneurons in the basolateral amygdala that silence extinction neurons, thus restoring fear responses.

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