Neuronal Signalling of Fear Memory

Maren, S. & Quirk, G.J. (November 2004). Neuronal Signalling of Fear Memory. Nature Reviews Neuroscience, 5, 844-850.

Plasticity within the CNS is necessary for the representation of new information, and can range from synthesis and insertion of synaptic proteins to whole-brain synchronization of neuronal activity. Pavlovian fear conditioning is an especially interesting phenomenon since such fear memories are acquired rapidly and are long-lasting. Research first noticed conditioning-induced changes in the midbrain, thalamus, and cortex; however, it was unclear whether or not these were primary sites of plasticity or were simply downstream from other plastic sites. Eventually the lateral nucleus of the amygdala (LA), receiving direct projections from the auditory thalamus, was posited to be vital for auditory fear conditioning. The dorsal subdivision of the nucleus (LAd) seems to be the first site in the auditory pathway to show associative plasticity that is not fed forward passively from upstream sites, is not dependent on downstream sites, and is crucial for conditioned behavior. And LA neurons appear to drive plasticity at both thalamic and cortical levels.

Fear memories are useful to anticipate and respond to dangers within the environment. However, when signals for aversive events no longer predict those events, fear to those signals subsides. This is an inhibitory learning process known as extinction. It appears that although fear subsides after extinction, the fear memory is not erased. Extinction seems to be highly context dependent and sometimes short-lived. Fear responses can be spontaneously recovered over time. It seems biology has deemed it better to fear than not to fear. It is more likely that additional memories which interfere with pre-existing excitatory responses are learned in the extinction process. Again the amygdala seems to be essentially involved here. Further, the mPFC, which has an inhibitory influence on both the LA and the CE (the main output regions of the amygdala) through a rich network of inhibitory interneurons embedded in the amygdala, appears to be a major participant, and is perhaps modulated by context via hippocampus.