The amygdala and medial prefrontal cortex: partners in the fear circuit

Abstract

Fear conditioning and fear extinction are Pavlovian conditioning paradigms extensively used to study the mechanisms that underlie learning and memory formation. The neural circuits that mediate this learning are evolutionarily conserved, and seen in virtually all species from flies to humans. In mammals, the amygdala and medial prefrontal cortex are two structures that play a key role in the acquisition, consolidation and retrieval of fear memory, as well extinction of fear. These two regions have extensive bidirectional connections, and in recent years, the neural circuits that mediate fear learning and fear extinction are beginning to be elucidated. In this review, we provide an overview of our current understanding of the neural architecture within the amygdala and medial prefrontal cortex. We describe how sensory information is processed in these two structures and the neural circuits between them thought to mediate different aspects of fear learning. Finally, we discuss how changes in circuits within these structures may mediate fear responses following fear conditioning and extinction. Fear is an evolutionarily conserved behavioural response that is essential for survival. Studies of fear have used the paradigm of classical fear conditioning in which an emotionally neutral stimulus, the conditioned stimulus (CS), such as a light or tone, is temporally paired with an aversive stimulus, the unconditioned stimulus (US), typically a footshock. Following a small number of pairings, subjects form an association between the CS and US, and learn to respond to the CS with an avoidance response, the conditioned response (CR), which is rapidly acquired and long lasting. However, subsequent presentations of the CS that are not paired with the US Roger Marek (left), Cornelia Strobel, Tim Bredy and Pankaj Sah (right) all work at the Queensland Brain Institute in Brisbane, Australia. RM and CS have both just completed their PhD and TB and PS are group leaders in the institute. They share an interest in the mechanisms that underlie learning and memory formation in fear conditioning and extinction. Between the two labs they use a combination of electrophysiology, molecular and behavioural analysis. Their areas of interest are varied and this review comes from their common their interests in the roles of the prefrontal cortex and amygdala. break this association, and lead to a gradual reduction of the CR through a process known as extinction. Since the first studies of Pavlov, it has been appreciated that extinction does not result from erasure of previous memory associated with the CS but is due, at least in part, to new learning (Pavlov, 1927). This idea rests on three key observations. First, the learnt fear response to the CS can reappear with the passage of time (spontaneous recovery). Secondly, the CR returns when the CS is presented in a context different from the one in which extinction training originally took place (renewal). Finally, unexpected delivery of the US following extinction can

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“…The infralimbic medial prefrontal cortex (IL) and basolateral amygdala (BLA) are implicated in acquisition of conditioned fear responses [102]. Moreover, plasticity in these regions is believed to mediate reversal of conditioned fear responses with extinction [103,104].…”

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“…Such exposures interrupt ongoing activities (Church, 1959), increase depression and anxiety-like behaviors (Warren et al, 2013), and elicit fear learning (Chen et al, 2009;Jeon et al, 2010;Yusufishaq and Rosenkranz, 2013). Emotionally salient stimuli generally recruit the dorsomedial prefrontal cortex (dmPFC) and the basolateral amygdala (BLA), which have strong reciprocal projections (Hubner et al, 2014;McDonald, 1998) and are involved in fear learning (Gilmartin et al, 2014;Marek et al, 2013;Senn et al, 2014), including contextual learning during observational fear (Amano et al, 2010;Jeon et al, 2010). Fear learning increases oscillatory synchronization between the two structures (Lesting et al, 2011;Likhtik et al, 2014;Stujenske et al, 2014), the amplitude of which correlates with the strength of fear memory (Popa et al, 2010).…”

The role of the basolateral amygdala in punishment

“…Using Pavlovian fear conditioning with a shock US, a variety of lines of evidence implicate the amygdala in aversive reinforcement (Maren and Quirk 2004). Principal cells of lateral and basolateral nuclei (BLA) receive glutamatergic inputs from thalamus and cortex conveying information about the CS and US (Sah et al 2003;Marek et al 2013). The strength of these inputs varies as a consequence of learning so that CS inputs are strengthened (Maren and Quirk 2004), whereas US inputs are weakened (Johansen et al 2010).…”