Oxytocin receptor binding in the titi monkey hippocampal formation is associated with parental status and partner affiliation

Abstract

Social cognition is facilitated by oxytocin receptors (OXTR) in the hippocampus, a brain region that changes dynamically with pregnancy, parturition, and parenting experience. We investigated the impact of parenthood on hippocampal OXTR in male and female titi monkeys, a pair-bonding primate species that exhibits biparental care of offspring. We hypothesized that in postmortem brain tissue, OXTR binding in the hippocampal formation would differ between parents and non-parents, and that OXTR density would correlate with frequencies of observed parenting and affiliative behaviors between partners. Subjects were 10 adult titi monkeys. OXTR binding in the hippocampus (CA1, CA2/3, CA4, dentate gyrus, subiculum) and presubiculum layers (PSB1, PSB3) was determined using receptor autoradiography. The average frequency of partner affiliation (Proximity, Contact, and Tail Twining) and infant carrying were determined from longitudinal observations (5-6 per day). Analyses showed that parents exhibited higher OXTR binding than non-parents in PSB1 (t₍₈₎ = - 2.33, p = 0.048), and that OXTR binding in the total presubiculm correlated negatively with Proximity (r = - 0.88) and Contact (r = - 0.91), but not Tail Twining or infant carrying. These results suggest that OXTR binding in the presubiculum supports pair bonding and parenting behavior, potentially by mediating changes in hippocampal plasticity.

Figure 1

Schematic of hippocampus and presubiculum brain regions quantified. The figure shows two adjacent sections from one representative titi monkey brain. The section in (a) was stained using Nissl staining. The section in (b) underwent ¹²⁵I-OVTA autoradiography to identify OXTR binding. (c,d) A zoomed in segment of (b) (the zoomed region is indicated by the black box). (c) The brain regions that were quantified, and (d) depicts the boundaries that were traced to quantify each brain region. ¹²⁵I-OVTA ¹²⁵I-ornithine vasotocin analog, CA1, CA2/3, CA4 CA fields of the hippocampus, DG dentate gyrus, Subic subiculum, PSB1 presubiculum layer 1, PSB3 presubiculum layer 3.

Figure 2

Parents exhibit higher OXTR binding density in PSB1. The top panel (a) shows the average OXTR binding density for parents and non-parents in each brain region quantified, and error bars indicate ± 1 standard error. *The group comparison is significant at p < 0.05. The bottom panel (b) shows a zoomed view of the average OXTR binding density in PSB1 for parents and non-parents (bars), with the average OXTR binding for each subject (circles) overlaid on top. The error bars in this panel correspond to ± 1 standard error across the different sections that were averaged for each subject. dpm disintegrations per minute, CA1, CA2/3, CA4 CA fields of the hippocampus, DG dentate gyrus, Subic subiculum, Total Hipp total hippocampus area (including CA1, CA2/3, CA4, DG, and Subic) , PSB1 presubiculum layer 1, PSB3 presubiculum layer 3, total presubiculum total presubiculum area (including PSB1 and PSB3).

Figure 3

No sex differences in OXTR binding in the hippocampus or presubiculum. The top panel (a) shows the average OXTR binding density for males and females in each brain region quantified, and error bars indicate ± 1 standard error. †The p value for the group comparison is < 0.10. The bottom panel (b) shows a zoomed view of the average OXTR binding density in the dentate gyrus for males and females (bars), with the average OXTR binding for each subject (circles) overlaid on top. The error bars in this panel correspond to the ± 1 standard error across the different sections that were averaged for each subject. dpm disintegrations per minute, CA1, CA2/3, CA4 CA fields of the hippocampus, DG dentate gyrus, Subic subiculum, Total Hipp total hippocampus area (including CA1, CA2/3, CA4, DG, and Subic) , PSB1 presubiculum layer 1, PSB3 presubiculum layer 3, Tot. PSB total presubiculum area (including PSB1 and PSB3).

Figure 4

OXTR binding in the presubiculum is associated with affiliative behavior with the pair mate. The figure shows the associations between average OXTR binding density (in the total presubiculum, PSB1, and PSB3) and average Proximity (a), Contact (b), and Tail Twining (c). The vertical error bars represent ± 1 standard error across the affiliation data averaged for the subject, and the horizontal errors bars represent ± 1 standard error across the OXTR binding of each brain section averaged for the subject. *The linear association between OXTR binding and the average affiliation state was significant at p < 0.05, and remained significant when pair tenure was controlled; **the linear association between OXTR binding and the average affiliation state was significant at p < 0.05 and remained significant when analyzed using Spearman rho rank correlation and when pair tenure was controlled; †the linear association between OXTR binding was not significant (p ranged from 0.11 to 0.25). For a full summary of the analyses, see Table 2. dpm disintegrations per minute, PSB1 presubiculum layer 1, PSB3 presubiculum layer 3, Total presubiculum total presubiculum area (including PSB1 and PSB3).