Prefrontal pathways target excitatory and inhibitory systems in memory-related medial temporal cortices

The anterior cingulate cortex (ACC), situated in the caudal part of the medial prefrontal cortex, is involved in monitoring on-going behavior pertaining to memory of previously learned outcomes. How ACC information interacts with the medial temporal lobe (MTL) memory system is not well understood. The present study used a multitiered approach to address two questions on the interactions between the ACC and the parahippocampal cortices in the rhesus monkey: (1) What are the presynaptic characteristics of ACC projections to the parahippocampal cortices? (2) What are the postsynaptic targets of the pathway and are there laminar differences in innervation of local excitatory and inhibitory systems? Labeled ACC terminations were quantified in parahippocampal areas TH and TF and a cluster analysis showed that boutons varied in size, with a population of small (≤0.97 microm) and large (>0.97 microm) terminations that were nearly evenly distributed in the upper and deep layers. Exhaustive sampling as well as unbiased stereological techniques independently showed that small and large boutons were about evenly distributed within cortical layers in the parahippocampal cortex. Synaptic analysis of the pathway, performed at the electron microscope (EM), showed that while most of the ACC projections formed synapses with excitatory neurons, a significant proportion (23%) targeted presumed inhibitory classes with a preference for parvalbumin (PV+) inhibitory neurons. These findings suggest synaptic mechanisms that may help integrate signals associated with attention and memory.