Topographic Mesocortex-Amygdalar Projections Expand the Molecular and Functional Model of the Limbic System

The limbic connectome is responsible for emotional evaluation and behavioral response to external and internal stimuli. Anxiety, depression, phobias and posttraumatic stress are mental disorders caused by the dysfunction of this system. We compared the pattern of anterograde projections of the full limbic mesocortical ring and the isocortex onto the glutamatergic/pallial amygdala. We used the amygdalar radial model, confirmed by transcriptomic studies, as well as anterograde connectivity experiments published in the Allen Brain Mouse Connectivity Atlas public database ( https://connectivity.brain-map.org/ ). The radial amygdalar model subdivides the glutamatergic amygdala into radial histogenetic-molecularly defined superdomains, domains and subdomains, each stratified in periventricular, intermediate and superficial nuclei. The mesocortical ring projections center onto the basolateral radial amygdalar subdomain and constitute a fundamental pathway in the limbic connectome, whereas the isocortical amygdalar input centers on the lateral radial unit. The mesocortical projections show a medial to lateral topographical distribution between the medial and lateral subdivisions of the basolateral amygdala. Intra-amygdalar connections suggest that computations in the lateral and anterior amygdalar radial domains add layers of complexity to the functions of the basolateral unit. The medial posterior orbitary cortex, proposed previously as the integrative node of the mesocortical ring, projects onto the medial basolateral amygdalar subunit, pointing to this neural structure as an important hub of the limbic system.