Pathways linking amygdala, hippocampus and anterior cingulate cortex in emotion, cognition and memory
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The interaction of emotion and memory is necessary for establishing a cognitive map including current context and past experiences, which is used by prefrontal cortex to regulate the internal state and guide goal directed actions and decision making. The amygdala, hippocampus and anterior cingulate cortex (ACC) play critical roles in these processes, but the organization of pathways between them is largely unknown in primates. This issue was addressed using neural tracers in rhesus monkeys to label the bidirectional pathways between amygdala and hippocampus and the unidirectional pathway from hippocampus to ACC. The amygdala sent a robust projection to hippocampus that formed large and closely spaced dual synapses on spines from the same dendritic segment, suggesting a strong influence. Further, amygdalar axon boutons innervated some disinhibitory calretinin neurons in CA1, suggesting enhanced excitatory influence. In contrast, in CA3 the amygdala pathway innervated calretinin and some of the powerful parvalbumin inhibitory neurons, which may help enhance memory of affective events. The reverse pathway from hippocampus densely and mainly targeted the ventro-medial part of the amygdala, including the basolateral (BL) and paralaminar basolateral (PLBL) nuclei. Hippocampal terminations formed synapses mostly on spines vii of presumed excitatory neurons. Some hippocampal terminations innervated inhibitory neurons in BL and PLBL and showed a rank of preference, by targeting mostly calretinin, and then calbindin and least parvalbumin inhibitory neurons. This pattern of innervation may allow contextual information represented by hippocampus to influence affective processes in the amygdala. The hippocampus sent strong projections to ACC (A32, A24a and A25) and targeted particularly A25, suggesting a role in affective and autonomic regulation. About 90% of hippocampal terminations in A25 innervated excitatory neurons, suggesting strong excitatory effects. The hippocampal pathway had a close relationship with postsynaptic D1 receptors in A25, especially in the deep layers. Dopamine has a strong influence in goal-directed actions, rewards, and attention in prefrontal cortex in primates, and may facilitate contextual information from the hippocampus to A25 to influence emotional regulation. The pathways studied were distinct, and suggest specific roles in emotional memory by the amygdala in hippocampus, in flexible learning and forgetting fear based on context transmitted from hippocampus to the amygdala, and in the synthesis of current context and past experience carried out by the hippocampal pathway to ACC to influence adaptive goal directed behavior.