The ventral striatum mediates goal-directed behaviors based, in part, on inputs from the amygdala. However, striatal areas caudal to the ventral striatum also receive inputs from the amygdala. In primates, the amygdala projects to the central ventral putamen, lateral amygdalostriatal area, and caudal ventral putamen, suggesting that these regions are also "limbic-related." The anterior insula, which integrates sensory and amygdaloid inputs, projects to the classic ventral striatum. We used retrograde and anterograde tract tracing techniques to determine the extent to which specific subdivisions of the insula influence the caudal ventral striatum in the primate. The anterior (agranular and rostral dysgranular) insula has significant inputs to caudal ventral striatal regions that receive projections from the amygdala. In contrast, the posterior (granular) insula has sparse projections. Within the agranular insula, the posteromedial agranular (Iapm), lateral agranular (Ial), and posterolateral agranular (Iapl) subdivisions have the strongest inputs. These subdivisions mediate olfactory, gustatory, and visceral information processing (Carmichael and Price JL [1996b] J. . In contrast, the intermediate agranular subdivision (Iai) is relatively devoid of visceral/gustatory inputs and has few inputs. In summary, caudal ventral striatal areas that receive amygdaloid inputs also receive significant innervation by agranular and dysgranular insula subdivisions that are themselves connected with the amygdala. Within this projection, the Ial, Iapm, and Iapl make the strongest contribution, suggesting that highly processed visceral/autonomic information, taste, and olfaction influence behavioral responses mediated by the caudal ventral striatum. Keywordslimbic; gustatory; caudate; putamen; amygdalostriatal area; amygdala; tract tracingThe rostral ventral striatum is considered a substrate for goal-directed behaviors based on its inputs from multiple brain regions mediating motivation and reward (Mogenson et al., 1980;Nauta, 1986;Ferry et al., 2000;Haber et al., 2000). However, it is increasingly recognized that caudal ventromedial striatal regions also receive inputs from several "limbic" brain regions, including the amygdala and anterior cingulate cortex (Russchen et al., 1985;Selemon and Goldman-Rakic, 1985;Nauta, 1986;McDonald et al., 1999;Ferry et al., 2000; ShammahLagnado et al., 2001;Fudge et al., 2004). We have previously defined the primate "caudal ventral striatum" based on amygdaloid afferent inputs and histochemical markers typical of the ventral striatum (Fudge and Haber, 2002;Fudge et al., 2004). Based on these criteria, the NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript caudal ventral striatum includes the ventromedial putamen surrounding, and caudal to, the decussation of the anterior commissure, the lateral amygdalostriatal area, and the medial tail of the caudate nucleus.The anterior insula is involved in emotional and multisensory processing (Lane et al., 1997;Phillips et a...

The ventral striatum mediates goal-directed behavior through limbic afferents. One well-established afferent to the ventral striatum is the amygdaloid complex, which projects throughout the shell and core of the nucleus accumbens, the rostral ventromedial caudate nucleus, and rostral ventromedial putamen. However, striatal regions caudal to the anterior commissure also receive inputs from the amygdala. These caudal areas contain histochemical and cytoarchitectural features that resemble the shell and core, based on our recent studies. Specifically, there is a calcium binding protein (CaBP)-poor region in the lateral amygdalostriatal area that resembles the "shell." To examine the idea that the caudal ventral striatum is part of the "classic" ventral striatum, we placed small injections of retrograde tracers throughout the caudal ventral striatum/amygdalostriatal area and charted the distribution of specific amygdaloid inputs. Amygdaloid inputs to the CaBP-poor zone in the lateral amygdalostriatal area arise from the basal nucleus, the magnocellular subdivision of the accessory basal nucleus, the periamygdaloid cortex, and the medial subdivision of the central nucleus, resembling that of the shell of the ventral striatum found in our previous studies. There are also amygdaloid inputs to CaBP-positive areas outside the shell, which originate mainly in the basal nucleus. Taken together, the "limbic-related" striatum forms a continuum from the rostral ventral striatum through the caudal ventral striatum/lateral amygdalostriatal area based on histochemical and cellular similarities, as well as inputs from the amygdala. Keywordsshell; nucleus accumbens; central nucleus; amygdalostriatal area; extended amygdala; limbicThe concept of the "ventral striatum" originated with Heimer (Heimer and Wilson, 1975;Heimer, 1978) and has been further elaborated over the last decade. In addition to the "nucleus accumbens," the ventromedial caudate nucleus and ventromedial putamen are considered part of the ventral striatum in primates, based on afferent inputs from brain regions mediating motivation and reward (Haber et al., 1995;Chikama et al., 1997;Kunishio and Haber, 1994). Consistent with its anatomic connections, the ventral striatum mediates operant responses to natural and drug rewards (Dickinson, 1994;Kelley and Holahan, 1997;Corbit et al., 2001). Functional neuroimaging studies confirm that the ventral striatum is involved in goal-directed behaviors in humans, for example, in tasks involving financial or other rewards (Koepp et al., 1998;Elliott et al., 2000;Breiter et al., 2001). Across species, the ventral striatum contains a unique subregion known as the "shell," which is tightly connected to the limbic system (Kunishio and Haber, 1994;Haber et al., 1995 1995;Chikama et al., 1997;Haber et al., 2000). The shell is best characterized by its relatively low levels of calbindin-D28k immunoreactivity but is also distinguished by other cytoarchitectural and histochemical features (Meredith et al., 1996;Heimer et al., 199...