Pathways for Contextual Memory: The Primate Hippocampal Pathway to Anterior Cingulate Cortex

Abstract

The anterior cingulate cortex (ACC) is one of the few prefrontal areas that receives robust direct hippocampal terminations. This pathway may enable current context and past experience to influence goal-directed actions and emotional regulation by prefrontal cortices. We investigated the still ill-understood organization of the pathway from anterior hippocampus to ACC (A24a, A25, A32) to identify laminar termination patterns and their postsynaptic excitatory and inhibitory targets from system to synapse in rhesus monkeys. The densest hippocampal terminations targeted posterior A25, a region that is involved in affective and autonomic regulation. Hippocampal terminations innervated mostly excitatory neurons (~90%), suggesting strong excitatory effects. Among the smaller fraction of inhibitory targets, hippocampal terminations in A25 preferentially innervated calretinin neurons, a pattern that differs markedly from rodents. Further, hippocampal terminations innervated spines with D1 receptors, particularly in the deep layers of A25, where D1 receptors are enriched in comparison with the upper layers. The proximity of hippocampal terminations to D1 receptors may enable dopamine to enhance information transfer from the hippocampus to A25 and contribute to dopaminergic influence downstream on goal-directed action and emotional control by prefrontal cortices, in processes that may be disrupted by excessive dopamine release during uncontrollable stress.

Keywords: anterior cingulate cortex; contextual memory; dopamine; hippocampus; inhibitory neurons.