Emotional intensity can enrich or degrade memories: impact of the amygdalar pathway on hippocampus through inhibitory neurons

Abstract The brain’s emotional system powerfully modulates processing of context and episodic memory. A key pathway that mediates these effects is the projection from the amygdala to the hippocampus. Wang and Barbas (1) uncovered a distinctive pattern in the pathways from amygdala to hippocampus in primates. In hippocampal CA3, a pathway from the amygdala innervated excitatory pyramidal neurons as well as parvalbumin (PV) and calretinin (CR) inhibitory neurons. In hippocampal CA1, amygdalar projections also innervated pyramidal neurons and CR interneurons, but not PV interneurons. The effects of these complex circuits can best be probed using computational simulations. We developed a model of spiking neurons to investigate the implications and significance of these amygdala-hippocampal circuits for affective influence on processing mnemonic context, and to test their effects as input from the amygdala gradually increased. Our simulations revealed that moderate input from the amygdala can enhance detail in CA3 representations that can correctly sort out contexts and episodes from memory. However, high amygdalar input suppressed CA3 responses to non-amygdalar inputs through powerful inhibitory neurons, leading to memory representations that lack detail. Moreover, high amygdalar input prematurely hastened the timing of responses in CA1 occurring when the current situation broadly and non-specifically matched a remembered context. Amygdalar pathways to hippocampus enable a mechanism whereby affective signaling appropriately enhances hippocampal representations of remembered context. However, when amygdalar input is excessive in high emotional arousal, there is loss of memory detail and overgeneralization, as seen in post-traumatic stress disorder or pathologic phobias.