Elsevier

Behavioural Brain Research

Volume 322, Part A, 30 March 2017, Pages 123-137
Behavioural Brain Research

The effects of neonatal amygdala or hippocampus lesions on adult social behavior

https://doi.org/10.1016/j.bbr.2016.11.052Get rights and content

Abstract

The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age. Experimental animals interacted with two male and two female partners in two conditions – one in which physical access was restricted (the constrained social access condition) and a second in which physical access was unrestricted (the unconstrained social access condition). Across conditions and interaction partners, there were no significant effects of lesion condition on the frequency or duration of social interactions. As a group, the hippocampus-lesioned animals generated the greatest number of communicative signals during the constrained social access condition. Amygdala-lesioned animals generated more frequent stress-related behaviors and were less exploratory. Amygdala and hippocampus-lesioned animals demonstrated greater numbers of stereotypies than control animals. Subtle, lesion-based differences in the sequencing of behaviors were observed. These findings suggest that alterations of adult social behavior are much less prominent when damage to the amygdala occurs early in life rather than in adulthood.

Introduction

Classic studies of the primate amygdala point to its involvement in affective and social processing. When amygdala damage occurs in adulthood, primates fail to respond to threat and novelty in normative ways. While intact animals are wary of novel and threatening objects, animals with amygdala damage show no such wariness [1], [2], [3], [4], [5], [6], [7], [8]. This failure to appropriately assess the potential threat value of stimuli likely underlies patterns of hyper-sociality following amygdala damage [9]. Without an amygdala to signal that a conspecific is potentially threatening, adult animals with amygdala damage readily approach and interact with novel conspecifics (e.g. [10], [11], [12], [13], [14]). Studies of adult amygdala damage have left unanswered questions about the importance of the amygdala for the development of normal affective and social behavior. Evaluating whether or not the amygdala is required for the development of normal social behavior has been the focus of a unique, long-term longitudinal study that concludes with this report.

Accumulating evidence suggests that early amygdala damage does not disrupt the generation of species-typical primate social behaviors per se—that is, animals with damage to the amygdala can physically generate species-typical affective and social behaviors [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]. However, the effects of damage to the amygdala across development are largely unknown. To address these questions, we initiated a long-term, longitudinal study in 2001 in which a cohort of rhesus macaques received neurotoxic lesions of the amygdala or hippocampus at approximately two weeks of age and their affective and social behavior was accessed across their entire lives (e.g.,[15], [25], [26], [27], [28], [29], [30]). Both operated peers (animals who received neonatal hippocampus lesions) and intact peers served as controls in these studies. The present report provides evidence that social behavior during adulthood, following early damage to the amygdala, is largely intact and comparable to that of control animals. Animals were tested in the same setting that was previously used to evaluate the social behavior of adult animals with adult amygdala damage [10]. To that end, subjects met four novel animals (two males and two females) from the colony at the California National Primate Research Center (CNPRC) in two conditions—the first in which one animal was constrained in a small cage behind a metal grille, and the second in which both animals had unlimited access to each other.

Section snippets

Methods

Experimental procedures were developed in consultation with the staff at the California National Primate Research Center and protocols were approved by the University of California Davis Institutional Animal Care and Use Committee.

Histological findings

The histological analyses demonstrated that the lesions were largely as intended. Lesions for each of the animals analyzed in this paper are illustrated in Fig. 2 (amygdala cases) and Fig. 3 (hippocampus cases) and volumetric analyses of the amount of tissue loss is presented in Table 3, Table 4. These lesions generally resulted in extensive bilateral removal of the dentate gyrus, hippocampus, and subicular complex. On average 85% of the neurons in those areas were removed in the experimental

Discussion

The present set of observations demonstrates that early, selective damage to either the amygdala or hippocampus does not result in a radically altered pattern of adult social behavior. While there were subtle differences in stress-related behaviors, exploratory behaviors, stereotypies, and the sequencing of behavior, social behavior per se was entirely intact. In fact, amygdala-lesioned animals were essentially indistinguishable from controls when the frequencies and durations of social

Acknowledgments

This work was supported by funding from the National Institutes of Mental Health (R37MH57502 to DGA), and by the base grant of the California National Primate Research Center (OD011107). EBM was supported by K99MH10138 during preparation of this manuscript. We thank the veterinary and husbandry staff of the California National Primate Research Center for excellent care of the animal subjects. We also thank Dr. Pierre Lavenex, Mr. Jeffrey Bennett, and Ms. Pamela Tennant for surgical assistance

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