The effects of neonatal amygdala or hippocampus lesions on adult social behavior.
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.
Project description:Medial temporal lobe brain structures, such as the amygdala, play an important role in the normal perception and generation of emotional behavior. Little research, however, has assessed the role of such structures across the neurodevelopmental trajectory. We assessed emotional behavioral responses of rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at 2 weeks of age and sham-operated controls. At 9 and 18 months of age, animals interacted with novel objects that varied in visual complexity as a means of varying emotional salience. All animals behaved differently in the presence of visually simple, as compared to complex, objects, suggesting that they were sensitive to variation in emotional salience. Across both experiments, amygdala-lesioned animals appeared to be less behaviorally inhibited insofar as they explored all objects most readily. Interestingly, hippocampus-lesioned animals' propensity for exploration mirrored that of control animals in some contexts but that of amygdala-lesioned animals in other contexts. At 18 months of age, both amygdala-lesioned and hippocampus-lesioned animals were judged to be less fearful than controls during the testing procedure. Implications for understanding the neurobiology of emotional behavior are discussed.
Project description:Longitudinal analysis of animals with neonatal brain lesions enables the evaluation of behavioral changes during multiple stages of development. Interpretation of such changes, however, carries the caveat that permanent neural injury also yields morphological and neurochemical reorganization elsewhere in the brain that may lead either to functional compensation or to exacerbation of behavioral alterations. We have measured the long-term effects of selective neonatal brain damage on resting cerebral glucose metabolism in nonhuman primates. Sixteen rhesus monkeys (Macaca mulatta) received neurotoxic lesions of either the amygdala (n=8) or hippocampus (n=8) when they were two weeks old. Four years later, these animals, along with age- and experience-matched sham-operated control animals (n=8), were studied with high-resolution positron emission tomography (microPET) and 2-deoxy-2[(18)F]fluoro-d-glucose ([(18)F]FDG) to detect areas of altered metabolism. The groups were compared using an anatomically-based region of interest analysis. Relative to controls, amygdala-lesioned animals displayed hypometabolism in three frontal lobe regions, as well as in the neostriatum and hippocampus. Hypermetabolism was also evident in the cerebellum of amygdala-lesioned animals. Hippocampal-lesioned animals only showed hypometabolism in the retrosplenial cortex. These results indicate that neonatal amygdala and hippocampus lesions induce very different patterns of long-lasting metabolic changes in distant brain regions. These observations raise the possibility that behavioral alterations in animals with neonatal lesions may be due to the intended damage, to consequent brain reorganization or to a combination of both factors.
Project description:Acute illness not only reduces the expression of social behavior by sick rodents, but can also lead to avoidance responses when detected by healthy, would-be social partners. When healthy animals interact with a sick partner, an intriguing question arises: does exposure to a sick conspecific elicit an anticipatory immune response that would facilitate defense against future infection? To address this question, healthy adult male Sprague-Dawley rats (N=64) were given a brief social interaction (30min) with a partner that was either sick (250?g/kg injection with lipopolysaccharide [LPS] 3h prior to test) or healthy (sterile saline injection). During this exposure, social behavior directed toward the healthy or sick conspecific was measured. Additionally, the impact of housing condition was assessed, with rats group- or isolate-housed. Immediately after social interaction, brains were harvested for cytokine assessments within socially-relevant brain structures (olfactory bulb, amygdala, hippocampus and PVN). As expected, behavioral results demonstrated that (i) there was a robust suppression of social interaction directed against sick conspecifics; and (ii) isolate-housing generally increased social behavior. Furthermore, examination of central cytokine expression in healthy experimental subjects revealed a modest increase in TNF-? in rats that interacted with a sick social partner, but only in the olfactory bulb. Among the LPS-injected partners, expected increases in IL-1?, IL-6, and TNF-? expression were observed across all brain sites. Moreover, IL-1? and IL-6 expression was exacerbated in LPS-injected partners that interacted with isolate-housed experimental subjects. Together, these data replicate and extend our prior work showing that healthy rats avoid sick conspecifics, and provide preliminary evidence for an anticipatory cytokine response when rats are exposed to a sick partner. These data also provide new evidence to suggest that recent housing history potently modulates cytokine responses evoked by LPS.
Project description:Compensatory social behavior in nonhuman animals following maternal loss has been documented, but understanding of how orphans allocate bonding to reconstruct their social networks is limited. Successful social integration may be critical to survival and reproduction for highly social species and, therefore, may be tied to population persistence. We examined the social partners involved in affiliative interactions of female orphans and non-orphans in an elephant population in Samburu, northern Kenya that experienced heightened adult mortality driven by drought and intense ivory poaching. We contrasted partners across different competitive contexts to gain insight to the influence of resource availability on social interactions. Though the number of partners did not differ between orphans and non-orphans, their types of social partners did. Orphans interacted with sisters and matriarchs less while feeding than did non-orphans, but otherwise their affiliates were similar. While resting under spatially concentrated shade, orphans had markedly less access to mature adults but affiliated instead with sisters, bulls, and age mates. Orphan propensity to strengthen bonds with non-dominant animals appears to offer routes to social integration following maternal loss, but lack of interaction with adult females suggests orphans may experience decreased resource access and associated fitness costs in this matriarchal society.
Project description:Social behavior dysfunction is a symptomatic element of schizophrenia and autism spectrum disorder (ASD). Although altered activities in numerous brain regions are associated with defective social cognition and perception, the causative relationship between these altered activities and social cognition and perception-and their genetic underpinnings-are not known in humans. To address these issues, we took advantage of the link between hemizygous deletion of human chromosome 22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We genetically manipulated Sept5, a 22q11.2 gene, and evaluated its role in social interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a congenic genetic background, selectively impaired active affiliative social interaction in mice. Conversely, virally guided overexpression of Sept5 in the hippocampus or, to a lesser extent, the amygdala elevated levels of active affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from control mice in novelty and olfactory responses, anxiety or motor activity. Moreover, post-weaning individual housing, an environmental condition designed to reduce stress in male mice, selectively raised levels of Sept5 protein in the amygdala and increased active affiliative social interaction in C57BL/6J mice. These findings identify this 22q11.2 gene in the hippocampus and amygdala as a determinant of social interaction and suggest that defective social interaction seen in 22q11.2-associated schizophrenia and ASD can be genetically and environmentally modified by altering this 22q11.2 gene.
Project description:Previous studies have shown that the amygdala is important in processing not only animate entities but also social information. It remains to be determined to what extent the factors of category and social context interact to modulate the activities of the amygdala and cortical regions. In this study, pictures depicting animals and inanimate objects in negative and neutral levels were presented. The contexts of the pictures differed in whether they included human/human parts. The factors of valence, arousal, familiarity and complexity of pictures were controlled across categories. The results showed that the amygdala activity was modulated by category and contextual information. Under the nonhuman context condition, the amygdala responded more to animals than objects for both negative and neutral pictures. In contrast, under the human context condition, the amygdala showed stronger activity for negative objects than animals. In addition to cortical regions related to object action, functional and effective connectivity analyses showed that the anterior prefrontal cortex interacted more with the amygdala for negative objects (vs. animals) in the human context condition, by a top-down modulation of the anterior prefrontal cortex to the amygdala. These results highlighted the effects of category and human contexts on modulating brain activity in emotional processing.
Project description:The stimulation of adult hippocampal neurogenesis by antidepressants has been associated with multiple molecular pathways, but the potential influence exerted by other brain areas has received much less attention. The basolateral complex of the amygdala (BLA), a region involved in anxiety and a site of action of antidepressants, has been implicated in both basal and stress-induced changes in neural plasticity in the dentate gyrus. We investigated here whether the BLA modulates the effects of the SSRI antidepressant fluoxetine on hippocampal cell proliferation and survival in relation to a behavioral index of depression-like behavior (forced swim test). We used a lesion approach targeting the BLA along with a chronic treatment with fluoxetine, and monitored basal anxiety levels given the important role of this behavioral trait in the progress of depression. Chronic fluoxetine treatment had a positive effect on hippocampal cell survival only when the BLA was lesioned. Anxiety was related to hippocampal cell survival in opposite ways in sham- and BLA-lesioned animals (i.e., negatively in sham- and positively in BLA-lesioned animals). Both BLA lesions and low anxiety were critical factors to enable a negative relationship between cell proliferation and depression-like behavior. Therefore, our study highlights a role for the amygdala on fluoxetine-stimulated cell survival and on the establishment of a link between cell proliferation and depression-like behavior. It also reveals an important modulatory role for anxiety on cell proliferation involving both BLA-dependent and -independent mechanisms. Our findings underscore the amygdala as a potential target to modulate antidepressants' action in hippocampal neurogenesis and in their link to depression-like behaviors.
Project description:Adolescence is a neuroplastic period for self-processing and emotion regulation transformations, that if derailed, are linked to persistent depression. Neural mechanisms of adolescent self-processing and emotion regulation ought to be targeted via new treatments, given moderate effectiveness of current interventions. Thus, we implemented a novel neurofeedback protocol in adolescents to test the engagement of circuits sub-serving self-processing and emotion regulation. METHODS:Depressed (n?=?34) and healthy (n?=?19) adolescents underwent neurofeedback training using a novel task. They saw their happy face as a cue to recall positive memories and increased displayed amygdala and hippocampus activity. The control condition was counting-backwards while viewing another happy face. A self vs. other face recognition task was administered before and after neurofeedback training. RESULTS:Adolescents showed higher frontotemporal activity during neurofeedback and higher amygdala and hippocampus and hippocampi activity in time series and region of interest analyses respectively. Before neurofeedback there was higher saliency network engagement for self-face recognition, but that network engagement was lower after neurofeedback. Depressed youth exhibited higher fusiform, inferior parietal lobule and cuneus activity during neurofeedback, but controls appeared to increase amygdala and hippocampus activity faster compared to depressed adolescents. CONCLUSIONS:Neurofeedback recruited frontotemporal cortices that support social cognition and emotion regulation. Amygdala and hippocampus engagement via neurofeedback appears to change limbic-frontotemporal networks during self-face recognition. A placebo group or condition and contrasting amygdala and hippocampus, hippocampi or right amygdala versus frontal loci of neurofeedback, e.g. dorsal anterior cingulate cortex, with longer duration of neurofeedback training will elucidate dosage and loci of neurofeedback in adolescents.
Project description:It is generally believed that neural damage that occurs early in development is associated with greater adaptive capacity relative to similar damage in an older individual. However, few studies have surveyed whole brain changes following early focal damage. In this report, we employed multimodal magnetic resonance imaging analyses of adult rhesus macaque monkeys who had previously undergone bilateral, neurotoxic lesions of the amygdala at about 2 weeks of age. A deformation-based morphometric approach demonstrated reduction of the volumes of the anterior temporal lobe, anterior commissure, basal ganglia, and pulvinar in animals with early amygdala lesions compared to controls. In contrast, animals with early amygdala lesions had an enlarged cingulate cortex, medial superior frontal gyrus, and medial parietal cortex. Diffusion-weighted imaging tractography and network analysis were also used to compare connectivity patterns and higher-level measures of communication across the brain. Using the communicability metric, which integrates direct and indirect paths between regions, lesioned animals showed extensive degradation of network integrity in the temporal and orbitofrontal cortices. This work demonstrates both degenerative as well as progressive large-scale neural changes following long-term recovery from neonatal focal brain damage.
Project description:Early-life status epilepticus produces deficit in social interaction and vocalization, enhances anxiety, no cognitive impairment and alters functional connectivity within the hippocampus (CA3-CA1) and between the hippocampus and prefrontal cortex , , , , , , , , , , , , but the underlying mechanisms remain unknown. This data article contains behavioral and molecular data of the adult male Wistar rats subjected to early life pilocarpine-induced seizures. Animal's behaviors were assessed to social memory and social motivation, working and reference memories and cognitive flexibility. The brain tissues (hypothalamus, hippocampus, amygdala, and striatum) were probed to gene and protein expression of molecules related to social behavior, reward system and synaptic function.