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The contextual brain: implications for fear conditioning, extinction and psychopathology

Key Points

  • Contexts provide information that is central to understanding the meaning of events.

  • Studies of associative learning, including Pavlovian fear conditioning and extinction, in animal models and humans have revealed neural circuits for contextual information processing.

  • The hippocampus and medial prefrontal cortex are critical for encoding and retrieving contextual information. A major function of this circuit is in the disambiguation of cues that have different meanings in different contexts.

  • The neural circuits involved in processing discrete cues, such as conditional and unconditional stimuli, share some overlap with context circuits but are largely distinct.

  • Deficits in context processing and pathology in hippocampal–prefrontal circuits may accompany many forms of psychiatric illness, including post-traumatic stress disorder and substance abuse disorders.

Abstract

Contexts surround and imbue meaning to events; they are essential for recollecting the past, interpreting the present and anticipating the future. Indeed, the brain's capacity to contextualize information permits enormous cognitive and behavioural flexibility. Studies of Pavlovian fear conditioning and extinction in rodents and humans suggest that a neural circuit including the hippocampus, amygdala and medial prefrontal cortex is involved in the learning and memory processes that enable context-dependent behaviour. Dysfunction in this network may be involved in several forms of psychopathology, including post-traumatic stress disorder, schizophrenia and substance abuse disorders.

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Figure 1: Stimulus elements, context and memory.
Figure 2: Context encoding, conditioning and retrieval tasks in rodents.
Figure 3: Brain circuits involved in cue and context processing in the human brain.
Figure 4: Context-dependent extinction of fear in rodents.
Figure 5: Context-dependence of neuronal activity in the rat amygdala.
Figure 6: Neural circuit for context-dependent regulation of fear memory.

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Acknowledgements

Work from the authors' laboratories described in this paper is supported by grants from the US National Institutes of Health to S.M. (R01MH065961), K.L.P. (R01MH086517 and R01MH071698) and I.L. (R24MH075999).

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Maren, S., Phan, K. & Liberzon, I. The contextual brain: implications for fear conditioning, extinction and psychopathology. Nat Rev Neurosci 14, 417–428 (2013). https://doi.org/10.1038/nrn3492

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