Switching on and off fear by distinct neuronal circuits

Herry, C. et al. (2008). Switching on and off fear by distinct neuronal circuits. Nature, 454, 600-605.

Whereas firing of amygdala neurons is necessary for retrieval of conditioned fear memories, extinction of these fear memories is thought to be controlled by constraining this neural activity by local inhibitory circuitry (under the influence of mPFC). However, fear extinction is known to be a fragile behavioral state, readily influenced by context, i.e. changing context can result in spontaneous recovery. This raises the question of whether there are specialized circuits driving behavioral transitions in opposite directions, namely fear-on and fear-off. This paper showed that neurons in the BA could be divided into distinct functional classes: those exhibiting selective increases in CS+ evoked spike firing during and after fear conditioning (fear neurons) and those exhibiting selective increases in CS+ evoked spike firing during extinction (extinction neurons). Further, close analysis revealed that these two groups were not only functionally different but also differentially connected, with (1) fear neurons selectively receiving input from the hippocampus, and (2) extinction neurons being reciprocally connected to the mPFC while fear neurons only projected unidirectionally to the mPFC. This would indicate that co-localized within the same nucleus, two discrete neuronal circuits exist, intermingled in a salt-and-pepper-like manner. Their close anatomical proximity may serve to facilitate local interactions, although these mechanisms remain unexplored. Taken together with evidence showing emotional perseveration (persistent lack of state change) concomitant with inactivation of the BA, results suggest that the BA is unlikely to be associated with the storage, retrieval, or expression of conditioned fear and extinction memories, but is more likely to mediate context-dependent behavioral transitions between low and high fear states.