Encoding of contextual fear memory in hippocampal–amygdala circuit

Abstract

In contextual fear conditioning, experimental subjects learn to associate a neutral context with an aversive stimulus and display fear responses to a context that predicts danger. Although the hippocampal-amygdala pathway has been implicated in the retrieval of contextual fear memory, the mechanism by which fear memory is encoded in this circuit has not been investigated. Here, we show that activity in the ventral CA1 (vCA1) hippocampal projections to the basal amygdala (BA), paired with aversive stimuli, contributes to encoding conditioned fear memory. Contextual fear conditioning induced selective strengthening of a subset of vCA1-BA synapses, which was prevented under anisomycin-induced retrograde amnesia. Moreover, a subpopulation of BA neurons receives stronger monosynaptic inputs from context-responding vCA1 neurons, whose activity was required for contextual fear learning and synaptic potentiation in the vCA1-BA pathway. Our study suggests that synaptic strengthening of vCA1 inputs conveying contextual information to a subset of BA neurons contributes to encoding adaptive fear memory for the threat-predictive context.

High-frequency stimulation of ventral CA1 neurons reduces amygdala activity and inhibits fear

“…This result was somewhat surprising given the role of the ventral hippocampus in fear and anxiety and its strong connectivity with subcortical regions that are involved in emotion (Jimenez et al 2018;Hoover and Vertes 2007;Swanson 2006, 2007). However, a recent study found that vCA1 neurons activated during exploration are the same cells that increase their connectivity with basal amygdala neurons after the environment is paired with shock (Kim and Cho 2020). Together with the current results, these data suggest that the ventral hippocampus may primarily transmit context information to the amygdala during fear conditioning.…”

“…Therefore, our behavioral effects may be small because we did not selectively stimulate vCA1 neurons that were activated during training. These "engram cells" were recently shown to increase their connectivity with BA neurons after context fear conditioning (Kim and Cho 2020). It is possible, therefore, that low-frequency stimulation of vCA1 "engram cells" would enhance freezing after training.…”

“…During context fear conditioning, spatial information is transmitted from dorsal to ventral hippocampus and then relayed to the amygdala where it is associated with shock (Wiltgen et al 2006;Sutherland et al 2008;Maren and Fanselow 1995;Xu et al 2016;Jimenez et al 2018;Kim and Cho 2020). We examined the relationship between fear expression and activity in the ventral hippocampus to amygdala pathway.…”

Bidirectional regulation of cognitive and anxiety-like behaviors by dentate gyrus mossy cells in male and female mice

“…The sections were then incubated overnight at 4 °C in rabbit polyclonal anti-c-Fos primary antibody (1:2000, #226003, Synaptic Systems) diluted in blocking solution. This antibody is widely used and highly specific for c-Fos protein (Zhou et al, 2019;Kim and Cho, 2020). On the following day, sections were rinsed in 0.1 M TB (3 x 5 minutes) and incubated in biotinylated goat anti-rabbit secondary antibody (1:500, Vector) diluted in Tris B for 2 hours.…”

Independence of Cued and Contextual Components of Fear Conditioning is Gated by the Lateral Habenula

“…In normal conditions, that processing leads to a double association that assigns a predictive value to both the context and the cues. Prevailing models postulate that context-US association involves context encoding circuits centered in the hippocampus which send contextual representation to the amygdala where the association takes place (W. Bin Kim & Cho, 2020;Maren et al, 2013), and locate cue-US association in the amygdala (Bocchio et al, 2017). Particularly, solid evidence indicates that tone-US association takes place in cortical and thalamic auditory inputs to the lateral amygdala (Nabavi et al, 2014;Rumpel et al, 2005;Sah et al, 2008).…”