The naked mole-rat (Heterocephalus glaber) demonstrates a strict social and reproductive hierarchy. Oxytocin (OXT) is a peptide hormone that acts both peripherally and centrally in the regulation of a number of sexual and social behaviours. The main area of central production of this peptide is the paraventricular nucleus of the hypothalamus (PVN). The present study characterized differences that exist in OXT neurons in this region. Breeders and subordinates from established colonies were sacrificed and brains were processed for OXT-immunoreactivity. Four further groups of paired animals underwent various social and hormonal manipulations (opposite-sex paired, same sex-paired, opposite-sex/gonadectomised paired, opposite-sex/vasectomized paired) and were also used for analysis. Results showed that subordinate naked mole-rats had significantly more OXT-immunoreactive neurons in the PVN than either breeders or paired animals that had been gonadectomised. However, no differences were found on measures of OXT cell volume. Possible functional significance of these differences is discussed.

Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / "August 2000." Typescript. Vita. Includes bibliographical references (leaves 189-210). Also available on the Internet.

published_or_final_version / abstract / toc / Anatomy / Doctoral / Doctor of Philosophy

<p>The visual world is full of potentially important information, but only a subset of the world can be evaluated at any time. An essential function of the central nervous system is to rapidly and adaptively select which stimuli warrant attention. Much of the time, attention is directed towards stimuli that are relevant for current goals. However, things that have proven important in an organisms' personal or evolutionary past effectively compete with goal-relevant targets for attention. In humans, one example of this attentional superset is faces: faces attract attention even when they are in competition with immediate goals. Using a combination of behavioral, pharmacological, and electrophysiological techniques in the rhesus macaque, I investigated the physiological, neurobiological, and evolutionary determinants of the attentional capture of faces. First, I show that the prioritization of faces is evolutionarily conserved in primates. Face distractors also capture attention in rhesus macaques, a species of old world monkey, successfully competing with task goals for limited attentional resources. Importantly, the same classes of faces have the greatest attentional effects in both monkeys and humans. Further, I describe behavioral evidence that subcortical systems contribute to the attentional salience of faces in this species, proving an initial characterization of the neural mechanisms that may mediate this effect. Next, I examine the interaction between pupil size and vigilance for faces. A focal increase in luminance has long been known to provoke pupil constriction, but here I show that the pupil response to a flashed distractor is proportional to the allocation of attention to that image. Pupil constriction may provide a novel implicit metric of stimulus attention. In particular, face images provoked greater pupil constriction than non-face images. Moreover, I also find that baseline pupil size is a strong predictor of distractor interference, suggesting that arousal may modulate social vigilance. Therefore, I next examined the activity of single neurons within dorsal anterior cingulate cortex (dACC), a region implicated in task performance across a wide variety of tasks, but which also has strong connections to subcortical neuromodulatory centers responsible for regulating arousal. I find that the dACC discriminates between social and nonsocial distractors, scales with distractor attention, and predicts adjustments in arousal and vigilance state on upcoming trials. This is consistent with a model in which dACC supports task performance through regulating arousal. Finally, I turn to oxytocin (OT), a neuromodulatory hormone released during affiliative social interactions that is also implicated in regulating arousal. Though typically thought to generally enhance social attention, I report multiple circumstances in which OT suppresses, rather than enhances, vigilance for faces. This suggests a mechanism through which affiliative social interactions can reduce social vigilance, permitting more relaxed social interactions. Together, these results highlight an evolutionarily conserved neural circuit important for the adaptive, contextual modulation of reflexive face attention, a behavior that is compromised in both anxiety disorders and autism.</p> / Dissertation

While studies have examined risk factors and consequences of child maltreatment in general, relatively few have focused specifically on neglect, especially maternally perpetrated child neglect. This is despite evidence that neglect is the most common and most rapidly increasing form of maltreatment, with some of the most serious long-term effects on child development. Maternal neglect constitutes a substantial disturbance in the mother-child relationship. For this reason, after establishing the epidemiology of neglect at a population level, this thesis examines the neurobiology of patterns of mother-infant attachment using functional MRI. Disturbance in mother-infant attachment, in conjunction with family, social and societal risk and protective factors, constitutes the likely pathway to maternal neglect. Specific objectives were: 1) to describe the magnitude of the problem of maternal neglect in Australia, using longitudinal population-based studies; 2) to identify risk and protective factors associated with neglect, both in a high risk population of extremely low birth weight (ELBW) infants and a representative birth cohort; 3) to specifically explore whether breastfeeding was protective against maternally perpetrated neglect; 4) to examine the consequences of child neglect on infant cognitive development and head growth; and 5) to determine how maternal brain and endocrine responses differ according to patterns of adult attachment security. In Part A, two cohort studies examined the epidemiology of child abuse and neglect among mothers and their infants born at the Mater Mothers’ Hospital in Brisbane, Australia. Cohort databases were confidentially linked with official notifications of child abuse and neglect. The first cohort included 353 ELBW infants who were assessed at birth and at 1, 2 and 4 years of age. The second cohort included 7223 children whose mothers were enrolled prenatally into the Mater-University of Queensland Study of Pregnancy (MUSP), where data were collected at birth, 6 months, and 5 and 14 years. The initial ELBW study examined all reported notifications of neglect, while the MUSP study focused particularly on substantiated maternally perpetrated neglect and the protective effect of breastfeeding. These studies examined a broad range of social and biological predictors. Outcome variables for child neglect were examined in the ELBW cohort using cognitive z-scores and growth parameters. Analytic techniques included multivariate modelling. In Part B, the neurobiology of mother-infant attachment was examined by monitoring a cohort of 61 first-time mothers from Houston, Texas, over 4 study visits. The mothers’ attachment classifications were determined during pregnancy using the Adult Attachment Interview. At 6 months, mother-infant pairs were videotaped, and serum oxytocin measures collected before, during and after interaction. At 10 months, the mothers viewed pictures of their own and unknown infants during functional MRI scanning. The first report examined the brain responses of 28 mothers to happy, neutral and sad infant face cues. The next compared brain responses of 15 mothers with “secure” attachment patterns to 15 “insecure/dismissing” mothers, and also examined differences in peripheral oxytocin response to mother-infant interaction. Data were analysed using a general linear model and repeated measures ANOVA. Overall, more than 1 in 10 children were reported for suspected child maltreatment, 3-5% as a result of substantiated neglect and 3% with maternally perpetrated neglect, with higher rates seen in the ELBW cohort. Duration of breastfeeding was inversely associated with the odds of maternal neglect, with non-breastfeeding mothers almost 4 times more likely to neglect their child compared to mothers who breastfed for 4 or more months, after adjusting for covariates. Other significant risk factors for substantiated maternal neglect included low education, young maternal age, and race, which were also significant univariate predictors in the ELBW population. ELBW children exposed to neglect showed a progressive decline in cognitive functioning over the first 4 years of life, as well as a significantly reduced head circumference at 2 and 4 years. When mothers viewed their own infant’s faces, compared with an unknown infant, key dopamine-associated reward processing regions of the brain were activated, including the midbrain’s ventral tegmental area/substantia nigra, striatum and prefrontal cortex. Mothers with an insecure/dismissing type of attachment showed significantly less activation of these reward regions in response to both happy and sad own-infant faces. On viewing their own infant’s crying faces, these mothers showed activation of the anterior insula, a region involved in feelings of unfairness, pain and disgust. “Secure” mothers showed greater peripheral oxytocin responses during mother-infant interaction, which were correlated with activation of the pituitary/hypothalamic region of the brain, where oxytocin is produced and secreted. These findings confirm the magnitude of neglect as a public health concern, with identifiable consequences and specific risk and protective factors. The neurobiological studies identify neuroendocrine systems associated with mother-infant responses and patterns of adult attachment. Together, these studies theoretically link secure mother-infant attachment with brain reward activation and oxytocin response, breastfeeding success, and a reduced risk for maternal neglect. Implications for prevention and intervention, and future research plans, are discussed.

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Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1993. / Vita. Abstract. Includes bibliographical references (leaves 154-169). Also available via the Internet.

Thesis (Ph.D.)--Kent State University, 2006. / Title from PDF t.p. (viewed Sept. 19, 2006). Advisor: Eric Glasgow. Keywords: oxytocin; isotocin; vasopressin; vasotocin; hypothalamo-neurohypophysial system; hypothalamus; development; autism; Prader-Willi Syndrome; single-minded; orthopedia; arylhydrocarbon nuclear translocator; Brn2; POU; zebrafish; behavior; paraventricular nucleus; supraoptic nucleus; preoptic nucleus; diencephalon; suprachiasmatic nucleus; thyroid transcription factor; sonic hedgehog; NK 2 transcription factor related; distal-less homeobox gene; homeobox; homeodomain; morpholino Includes bibliographical references (p. 230-266).

Oxytocin release within the brain modulates several social behaviours in animals and humans. Moreover, low central oxytocin content has been linked to neuropsychiatric disorders, such as anxiety and autism. The exogenous administration of oxytocin has been proposed for therapeutic treatment, but oxytocin does not cross the blood-brain barrier (BBB) in physiologically significant amounts. An alternative approach to oxytocin administration is to stimulate central oxytocin release using melanocortins. Central administration of the naturally occurring melanocortin, α-MSH, has been shown to trigger somatodendritic oxytocin release in vitro. Unfortunately, endogenous melanocortins also do not penetrate the BBB in neuroactive amounts. In this study, I investigated whether systemic administration of synthetic melanocortin receptor 3/4 (MC3/4) agonist, Melanotan-II (MT-II), affects oxytocin neuronal activity and secretion in anaesthetised rats. I hypothesised that systemic administration of MT-II directly (centrally) acts on magnocellular oxytocin neurones to trigger somatodendritic oxytocin release from neurones of the supraoptic nucleus (SON) of the hypothalamus in vivo. Firstly, using double immunohistochemistry against Fos protein, a widely used marker for neural activity, and oxytocin, I showed that intravenous (i.v.; 1 mg/kg), but not intranasal (1 and 30 μg rat), administration of MT-II markedly induced Fos expression in magnocellular oxytocin neurones of the SON and paraventricular nuclei (PVN) of the hypothalamus, and this response was prevented by prior intracerebroventricular (i.c.v.) administration of the melanocortin antagonist, SHU-9119 (1 μg rat). In addition, brain areas receiving peripheral inputs which are involved in the regulation of oxytocin and vasopressin release were also analysed, showing that i.v. MT-II significantly increased Fos expression in the nucleus tractus solitarii (NTS), but not in circumventricular organs of the anteroventral third ventricle (AV3V) region. MT-II-induced Fos in the NTS was not prevented by the i.c.v. melanocortin antagonist. Then, using in vivo electrophysiology, I investigated whether i.v. administration of MT-II affects the electrical activity of SON neurones. Extracellular single-unit recordings from identified magnocellular neurones of the SON showed that MT-II significantly increased the firing rate in oxytocin neurones, however, no significant changes in firing rate were detected in vasopressin neurones. Finally, in vivo oxytocin release experiments showed that i.v. administration of MT-II did not trigger somatodendritic oxytocin release within the SON as measured by microdialysis and subsequent radioimmunoassay. Interestingly, the i.c.v. administration of MT-II (1 μg rat) also failed to trigger oxytocin release within the SON. The analysis of oxytocin content in plasma revealed that the change in oxytocin concentration was significantly greater in i.v. MT-II injected rats compared to vehicle-injected rats. Taken together, these results show that after i.v., but not intranasal, administration of MT-II, the activity of magnocellular neurones of the SON is increased. As previous studies showed that SON oxytocin neurones are inhibited in response to direct application of melanocortin agonists, the actions of i.v. MT-II are likely to be mediated, at least in part, indirectly by activation of inputs from the caudal brainstem.