Cortical granularity shapes the organization of afferent paths to the amygdala and its striatal targets in nonhuman primate

Abstract

The prefrontal cortex (PFC) and insula, amygdala, and striatum form interconnected networks that drive motivated behaviors. We previously found a connectional trend in which granularity of the ventromedial and orbital PFC/insula predicted connections to the amygdala, and also the breadth of amygdalo-striatal efferents, including projections beyond the classic ventral striatum. To further interrogate connectional relationships among the cortex, amygdala, and striatum, and to further define the limbic (amygdala-recipient) striatum, we conducted tract tracing studies in two cohorts of Macaques (Male n = 14, Female n = 1). We focused on the cortico-amygdalo-striatal (indirect) and cortico- limbic striatal (direct) paths originating in the entire PFC and insula. Larger data sets and a quantitative approach revealed cortical rules in which cortical granularity predicts the complexity and location of projections to both the basal nucleus of the amygdala and striatum. Remarkably, projections from cortical-like basal nucleus to the striatum followed similar patterns. In both direct and indirect paths to the limbic striatum, agranular cortices formed a foundational, broad projection, and were joined by inputs from progressively more differentiated cortices. In amygdalo-striatal paths, the ventral basal nucleus was the foundational input, with progressively more dorsal basal nucleus regions gradually adding inputs as the limbic striatum extended caudally. Together, the indirect and direct paths followed consistent principles in which cortical granularity dictated the strength and complexity of projections at their targets. Cluster analyses independently confirmed these connectional trends, and also highlighted connectional features that predicted termination in specific subregions of the basal nucleus and limbic striatum. Significance StatementThe limbic system broadly refers to brain circuits that coordinate emotional responses. Here, we investigate circuits of the amygdala, which are involved in coding the emotional value of external cues, and their influence on the striatum. Regions of prefrontal cortex and insula form gradients of overlapping inputs to the amygdalas basal nucleus, which feed forward to the striatum. Direct cortical inputs to these amygdala-recipient striatal areas are surprisingly organized according to similar principles, but subtly shift from the classic ventral striatum to the caudal ventral striatum. Together, these distinct subsystems--cortico-amygdala-striatal circuits and direct cortico-striatal circuits-- provide substantial opportunity for different levels of internal, sensory, and external experiences to be integrated within the striatum, a major motor-behavioral interface.