Insular and gustatory inputs to the caudal ventral striatum in primates.

The 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; Shammah-Lagnado 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 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 al., 1998; Chua et al., 1999; Small et al., 2001; Krolak-Salmon et al., 2003) and has prominent inputs to the classic ventral striatum (Chikama et al., 1997; Ferry et al., 2000). The anterior half of the insular cortex also has strong interconnections with the amygdala (Aggleton et al., 1980; Mufson et al., 1981; Carmichael and Price, 1996a) as well as an array of inputs from sensory and sensory association regions (Carmichael and Price, 1996b). Consistent with these afferent connections, the anterior insula is metabolically active during a variety of emotional experiences including disgust (Phillips et al., 1998; Krolak-Salmon et al., 2003; Heining et al., 2003; Wicker et al., 2003), fear (Schienle et al., 2002), and sadness (Lane et al., 1997; Damasio et al., 2000; Liotti et al., 2002). Early classic studies in monkeys and humans showed that stimulation of the anterior insula generates gustatory, autonomic, and visceral responses (Kaada et al., 1949; Penfield and Faulk, 1955; Hoffman and Rasmussen, 1953), suggesting that the insula links emotional states with internal responses (see reviews by Augustine, 1996; Mesulam, 2000). The anterior insula is composed of the agranular cortex, including the posterior orbital surface, and dysgranular cortex (Id) (Rose, 1928; Mesulam and Mufson, 1982; Carmichael and Price, 1994). More recently, the agranular insula has been subdivided into multiple territories based on unique cytoarchitectural, histochemical, and connectional properties (Carmichael and Price, 1994). These agranular insular subdivisions have differential connections to the specific subregions of the sensory cortex and thalamus (Carmichael and Price, 1996b). In contrast to the anterior insula, the posterior insula has a granular organization (Ig) and receives few inputs from the amygdala (Mesulam and Mufson, 1982; Aggleton et al., 1980; Mufson et al., 1981). Although previous studies show that both the agranular and dysgranular regions of the anterior insula have significant inputs to the classic ventral striatum in primates (Chikama et al., 1997; Ferry et al., 2000), there is little information on specific insular projections to caudal aspects of the “limbic-related” striatum. To investigate the extent to which the caudal ventral striatum is influenced by specific subdivisions of the insula, we charted the distribution of retrogradely labeled cells in the insular subdivisions following small injections of retrograde tracers into several caudal ventral striatal regions. Injection sites were classified as being in the “limbic-related” striatum if they resulted in labeled cells in the amygdala based on our previous analysis (Fudge et al., 2004). Anterograde tracers then were placed into the anterior insula to verify the data from retrograde studies.