Distribution of Serotonergic Transporter Innervation in the Nucleus Accumbens and Ventral Pallidum Is Highly Conserved Among Primates

Abstract

The nucleus accumbens (NAcc) and ventral pallidum (VP) are key nodes in the mesolimbic reward pathway that facilitate stimulus salience, including the regulation of social motivation and attachment. Primate species display variation in social behaviors, including different levels of impulsivity, bonding, and aggression. Previous research has implicated neuromodulation of the reward pathway in the differential expression of various social behaviors, suggesting that differences in neurotransmitter innervation may play a role in species-specific patterns. To explore this, we examined serotonergic innervation in the NAcc and VP among primates. We used stereology to quantify serotonin transporter-immunoreactive (SERT-ir) axon length density in the NAcc and VP of 13 primate species, including humans, great apes, and cercopithecid and platyrrhine monkeys. Our data show that serotonergic innervation density within both the NAcc and VP is highly conserved among species. This finding contrasts with our previous findings of higher levels of SERT-ir axons in the dorsal striatum of humans and great apes relative to monkeys, a human-specific increase in dopaminergic innervation within the NAcc and VP, and a human-specific increase of neuropeptide Y in the NAcc, highlighting the mosaic nature of innervation patterns among species.

Keywords: basal ganglia; human evolution; reward pathway; social behavior; striatum.

FIGURE 1

Diagram of relative proportions of three ascending serotonergic pathways in mouse, rat, long‐tailed macaque, and human with squirrel monkey. Diagram is based on separate studies in mouse (Muzerelle et al. 2016), rat and macaque (E. Azmitia and Gannon 1983), squirrel monkey and human (Parent et al. 2011), as well as human alone (Wallman et al. 2011). MLF, medial longitudinal fasciculus; DRCT, dorsal raphe cortical tract; MFB, medial forebrain bundle.

FIGURE 2

Photomicrographs showing Nissl‐stained sections including the NAcc in human‐56 (a, e), baboon‐12 (b, f), pig‐tailed macaque‐15 (c, g), and capuchin‐16 (d, h). Photomicrographs including the VP in chimpanzee‐36 (i, m), rhesus macaque‐14 (j, n), Japanese macaque‐9 (k, o), and cotton‐top tamarin‐9 (l, p). Each sampling region is indicated by a dashed line. Age in years is listed after each speciman. a.c., anterior commissure; C, caudate nucleus; P, putamen. All sections are 40‐µm thick. Scale = 1 cm.

FIGURE 3

Photomicrographs of SERT‐stained tissue within the NAcc for human‐25 (a), gorilla‐40 (b), pig‐tailed macaque‐15 (c), rhesus macaque‐11 (d), and common marmoset‐11 (e) as well as within the VP for human‐23 (f), chimpanzee‐26 (g), moor macaque‐10 (h), olive baboon‐9 (i), Japanese macaque‐19 (j), and cotton‐top tamarin‐6 (k). Images demonstrate the intensity of the immunostaining. Staining was robust in all species and showed many SERT‐ir varicose axons. Age in years is listed after each speciman. Magnification = 100×. Scale = 20 µm.

FIGURE 4

(a) Histograms showing Nv among species within the NAcc. Nv is lower for humans than for marmosets and tamarins, and Nv is lower for moor macaques than for marmosets and tamarins. (b) Box plots showing SERT ALv/Nv among species. SERT ALv/Nv in the NAcc is highly conserved.

FIGURE 5

(a) Histograms showing Nv among species within the VP. Nv is lower for moor macaques than owl monkeys, tamarins, and marmosets. (b) Box plots showing SERT ALv/Nv among species in the VP. SERT innervation density is higher for moor macaques than capuchins, owl monkeys, and marmosets.