Is Oxytocin "Nature's Medicine"?

Oxytocin is a pleiotropic, peptide hormone with broad implications for general health, adaptation, development, reproduction, and social behavior. Endogenous oxytocin and stimulation of the oxytocin receptor support patterns of growth, resilience, and healing. Oxytocin can function as a stress-coping molecule, an anti-inflammatory, and an antioxidant, with protective effects especially in the face of adversity or trauma. Oxytocin influences the autonomic nervous system and the immune system. These properties of oxytocin may help explain the benefits of positive social experiences and have drawn attention to this molecule as a possible therapeutic in a host of disorders. However, as detailed here, the unique chemical properties of oxytocin, including active disulfide bonds, and its capacity to shift chemical forms and bind to other molecules make this molecule difficult to work with and to measure. The effects of oxytocin also are context-dependent, sexually dimorphic, and altered by experience. In part, this is because many of the actions of oxytocin rely on its capacity to interact with the more ancient peptide molecule, vasopressin, and the vasopressin receptors. In addition, oxytocin receptor(s) are epigenetically tuned by experience, especially in early life. Stimulation of G-protein-coupled receptors triggers subcellular cascades allowing these neuropeptides to have multiple functions. The adaptive properties of oxytocin make this ancient molecule of special importance to human evolution as well as modern medicine and health; these same characteristics also present challenges to the use of oxytocin-like molecules as drugs that are only now being recognized. SIGNIFICANCE STATEMENT: Oxytocin is an ancient molecule with a major role in mammalian behavior and health. Although oxytocin has the capacity to act as a "natural medicine" protecting against stress and illness, the unique characteristics of the oxytocin molecule and its receptors and its relationship to a related hormone, vasopressin, have created challenges for its use as a therapeutic drug.

Rewritable fidelity: How repeated pairings and age influence subsequent pair-bond formation in male prairie voles.

The prairie vole has proven a valuable animal model for the neurobiological study of social monogamy and pair bonding. Previous research has focused almost exclusively on virgin prairie voles forming pair-bonds for the first time - a paradigm with limited relevance to human social behavior. In the present study, we used stud males to assess the impact of repeated pair-bond formation and dissolution on the behaviors and neurobiology relevant to subsequent pair-bond formation. Stud males were tested for behavioral and neurobiological effects of repeated pair-bonding after the 1st, 5th, and 10th pairing. Aged breeder males that experienced minimal pair-bond dissolution were included to control for the effects of aging. Results showed that male prairie voles readily form new pair-bonds after repeated pair-bond dissolution. In terms of social monogamy, old age was associated with males spending less time in close social contact with unfamiliar females. There were no effects of age nor number of lifetime pairings on depressive-like behavior or paternal behavior toward pups. Within the brain, the patterns of oxytocin (OTR) and vasopressin type 1a (V1aR) receptors were largely unaffected, with the following exceptions: 1) males with only a single pairing had higher OTR densities in the paraventricular thalamus and bed nucleus of the stria terminalis; 2) there was an age-related increase in the density of OTR in the caudate putamen and an age-related decline in the density of V1aR in the cortical amygdala. The present findings have translational relevance to human social behavior in the context of aging and social experience.

System-specific activity in response to Δ9 -tetrahydrocannabinol: a functional magnetic resonance imaging study in awake male rats.

The aim of this study was to assess the effects of two doses of Δ9 -tetrahydrocannabinol (THC, cannabis' main psychoactive agent) and vehicle on blood-oxygen-level dependent (BOLD) activity in drug-naïve, awake rats, in an effort to obtain a THC-specific map of activation in clinically-relevant regions and systems. Intraperitoneal injections of low dose of THC resulted in increased positive and negative BOLD signals compared to vehicle and high dose in areas rich in cannabinoid receptor 1, as well as throughout the pain and hippocampal neural systems. These results offer unique maps of activity, or 'fingerprints', associated with systemic THC administration, allowing for further comparisons with either additional doses or compounds, or between THC administration modalities (i.e. systemic vs. ingested vs. inhaled), which ultimately adds to the translatability assessment of THC-induced BOLD between animal and human studies.

High estrogen and chronic haloperidol lead to greater amphetamine-induced BOLD activation in awake, amphetamine-sensitized female rats.

The ovarian hormone estrogen has been implicated in schizophrenia symptomatology. Low levels of estrogen are associated with an increase in symptom severity, while exogenous estrogen increases the efficacy of antipsychotic medication, pointing at a possible interaction between estrogen and the dopaminergic system. The aim of this study is to further investigate this interaction in an animal model of some aspects of schizophrenia using awake functional magnetic resonance imaging. Animals receiving 17ß-estradiol and haloperidol were scanned and BOLD activity was assessed in response to amphetamine. High 17ß-estradiol replacement and chronic haloperidol treatment showed increased BOLD activity in regions of interest and neural networks associated with schizophrenia (hippocampal formations, habenula, amygdala, hypothalamus etc.), compared with low, or no 17ß-estradiol. These data show that chronic haloperidol treatment has a sensitizing effect, possibly on the dopaminergic system, and this effect is dependent on hormonal status, with high 17ß-estradiol showing the greatest BOLD increase. Furthermore, these experiments further support the use of imaging techniques in studying schizophrenia, as modeled in the rat, but can be extended to addiction and other disorders.

Oxytocin promotes functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioregulatory nuclei.

The neuropeptide oxytocin (OXT) facilitates prosocial behavior and selective sociality. In the context of stress, OXT also can down-regulate hypothalamic-pituitary-adrenal (HPA) axis activity, leading to consideration of OXT as a potential treatment for many socioaffective disorders. However, the mechanisms through which administration of exogenous OXT modulates social behavior in stressful environmental contexts are not fully understood. Here, we investigate the hypothesis that autonomic pathways are components of the mechanisms through which OXT aids the recruitment of social resources in stressful contexts that may elicit mobilized behavioral responses. Female prairie voles (Microtus ochrogaster) underwent a stressor (walking in shallow water) following pretreatment with intraperitoneal OXT (0.25mg/kg) or OXT antagonist (OXT-A, 20mg/kg), and were allowed to recover with or without their sibling cagemate. Administration of OXT resulted in elevated OXT concentrations in plasma, but did not dampen the HPA axis response to a stressor. However, OXT, but not OXT-A, pretreatment prevented the functional coupling, usually seen in the absence of OXT, between paraventricular nucleus (PVN) activity as measured by c-Fos immunoreactivity and HPA output (i.e. corticosterone release). Furthermore, OXT pretreatment resulted in functional coupling between PVN activity and brain regions regulating both sympathetic (i.e. rostral ventrolateral medulla) and parasympathetic (i.e. dorsal vagal complex and nucleus ambiguous) branches of the autonomic nervous system. These findings suggest that OXT increases central neural control of autonomic activity, rather than strictly dampening HPA axis activity, and provides a potential mechanism through which OXT may facilitate adaptive and context-dependent behavioral and physiological responses to stressors.

Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction.

The prevalence of autism spectrum disorder (ASD) is as high as 1 in 100 individuals and is a heavy burden to society. Thus, identifying causes and treatments is imperative. Here, we briefly review the topics covered in our 2012 Society for Neuroscience Mini-Symposium entitled "Integrative Approaches Using Oxytocin to Enhance Prosocial Behavior: From Animal and Human Social Behavior to ASD's Social Dysfunction." This work is not meant to be a comprehensive review of oxytocin and prosocial behavior. Instead, we wish to share the newest findings on the effects of oxytocin on social behavior, the brain, and the social dysfunction of ASD at the molecular, genetic, systemic, and behavior levels, in varied subjects ranging from animal models to humans suffering from autism for the purpose of promoting further study for developing the clinical use of oxytocin in treating ASD.

Animals in flow - towards the scientific study of intrinsic reward in animals.

The concept of flow, a state of complete absorption in an intrinsically rewarding activity, has played a pivotal role in advancing notions of human well-being beyond minimising suffering towards promoting flourishing and thriving. While flow has played a fundamental role in human positive psychology, it has not yet been explored in non-human animals, leaving an enormous void in our understanding of intrinsic motivation in animals. As ethology and related fields keep progressing in uncovering complex cognitive and affective capacities of non-human animals, we propose the time is ripe to translate the concept of flow to animals. We start by embedding flow in the topic of intrinsic motivation and describe its impact on positive human psychology and potentially positive animal welfare. We then disambiguate flow from related concepts discussed in the animal literature. Next, we derive experimental approaches in animals from the canonical characteristics of flow in humans and provide guidelines for both inducing and assessing flow by focusing on two characteristics that do not necessarily depend on self-report, namely resistance to distraction and time distortion. Not all aspects of the human flow experience are (yet) translatable, but those that are may improve quality of life in captive non-human animals.

Transcriptional diversity of the oxytocin receptor in prairie voles: mechanistic implications for behavioral neuroscience and maternal physiology.

The neurohormone oxytocin regulates many aspects of physiology primarily by binding to its receptor, the oxytocin receptor. The oxytocin receptor gene (Oxtr) has been shown to have alternative transcripts in the mouse brain which may each have different biological functions or be used in specific contexts. A popular animal model for studying oxytocin-dependent social behaviors is the prairie vole, a biparental and monogamous rodent. Alternative transcriptional capacity of Oxtr in prairie voles is unknown. We used 5' rapid amplification of cDNA ends to identify alternative Oxtr transcription start sites in prairie vole brain tissue and uterine tissue. We then validated expression of specific transcripts in fetal brains and assessed the impact of exogenous oxytocin administration in utero on offspring brain development. We identified seven distinct Oxtr transcripts, all of which are present in both brain and uterine tissue. We then demonstrated that maternal oxytocin administration alters expression of a specific subset of Oxtr transcripts and that these different transcripts are under unique epigenetic regulation, such that in the perinatal period only one of the alternative transcripts is associated with DNA methylation in the Oxtr promoter. These data establish the existence of multiple Oxtr transcripts in prairie vole brain and uterine tissue and implicate oxytocin in the regulation of alternative transcript expression. These data have significant implications for our understanding of null mutant models in both mice and voles and translation in human birth and behavior.

Neuroanatomical and functional consequences of oxytocin treatment at birth in prairie voles.

Birth is a critical period for the developing brain, a time when surging hormone levels help prepare the fetal brain for the tremendous physiological changes it must accomplish upon entry into the 'extrauterine world'. A number of obstetrical conditions warrant manipulations of these hormones at the time of birth, but we know little of their possible consequences on the developing brain. One of the most notable birth signaling hormones is oxytocin, which is administered to roughly 50% of laboring women in the United States prior to / during delivery. Previously, we found evidence for behavioral, epigenetic, and neuroendocrine consequences in adult prairie vole offspring following maternal oxytocin treatment immediately prior to birth. Here, we examined the neurodevelopmental consequences in adult prairie vole offspring following maternal oxytocin treatment prior to birth. Control prairie voles and those exposed to 0.25 mg/kg oxytocin were scanned as adults using anatomical and functional MRI, with neuroanatomy and brain function analyzed as voxel-based morphometry and resting state functional connectivity, respectively. Overall, anatomical differences brought on by oxytocin treatment, while widespread, were generally small, while differences in functional connectivity, particularly among oxytocin-exposed males, were larger. Analyses of functional connectivity based in graph theory revealed that oxytocin-exposed males in particular showed markedly increased connectivity throughout the brain and across several parameters, including closeness and degree. These results are interpreted in the context of the organizational effects of oxytocin exposure in early life and these findings add to a growing literature on how the perinatal brain is sensitive to hormonal manipulations at birth.

Differences in Diffusion-Weighted Imaging and Resting-State Functional Connectivity Between Two Culturally Distinct Populations of Prairie Vole.

BACKGROUND: We used the highly prosocial prairie vole to test the hypothesis that higher-order brain structure-microarchitecture and functional connectivity (FC)-would differ between males from populations with distinctly different levels of prosocial behavior. Specifically, we studied males from Illinois (IL), which display high levels of prosocial behavior, and first generation males from Kansas dams and IL males (KI), which display the lowest level of prosocial behavior and higher aggression. Behavioral differences between these males are associated with overexpression of estrogen receptor alpha in the medial amygdala and bed nucleus of the stria terminalis and neuropeptide expression in the paraventricular nucleus. METHODS: We compared apparent diffusion coefficient, fractional anisotropy, and blood oxygen level-dependent resting-state FC between males. RESULTS: IL males displayed higher apparent diffusion coefficient in regions associated with prosocial behavior, including the bed nucleus of the stria terminalis, paraventricular nucleus, and anterior thalamic nuclei, while KI males showed higher apparent diffusion coefficient in the brainstem. KI males showed significantly higher fractional anisotropy than IL males in 26 brain regions, with the majority being in the brainstem reticular activating system. IL males showed more blood oxygen level-dependent resting-state FC between the bed nucleus of the stria terminalis, paraventricular nucleus, and medial amygdala along with other brain regions, including the hippocampus and areas associated with social and reward networks. CONCLUSIONS: Our results suggest that gray matter microarchitecture and FC may play a role the expression of prosocial behavior and that differences in other brain regions, especially the brainstem, could be involved. The differences between males suggests that this system represents a potentially valuable model system for studying emotional differences and vulnerability to stress and addiction.

Functional Connectivity Differences Between Two Culturally Distinct Prairie Vole Populations: Insights Into the Prosocial Network.

BACKGROUND: The goal of this study was to elucidate the fundamental connectivity-resting-state connectivity-within and between nodes in the olfactory and prosocial (PS) cores, which permits the expression of social monogamy in males; and how differential connectivity accounts for differential expression of prosociality and aggression. METHODS: Using resting-state functional magnetic resonance imaging, we integrated graph theory analysis to compare functional connectivity between two culturally/behaviorally distinct male prairie voles (Microtusochrogaster). RESULTS: Illinois males display significantly higher levels of prosocial behavior and lower levels of aggression than KI (Kansas dam and Illinois sire) males, which are associated with differences in underlying neural mechanisms and brain microarchitecture. Shared connectivity 1) between the anterior hypothalamic area and the paraventricular nucleus and 2) between the medial preoptic area and bed nucleus of the stria terminalis and the nucleus accumbens core suggests essential relationships required for male prosocial behavior. In contrast, Illinois males displayed higher levels of global connectivity and PS intracore connectivity, a greater role for the bed nucleus of the stria terminalis and anterior hypothalamic area, which were degree connectivity hubs, and greater PS and olfactory intercore connectivity. CONCLUSIONS: These findings suggest that behavioral differences are associated with PS core degree of connectivity and postsignal induction. This transgenerational system may serve as powerful mental health and drug abuse translational model in future studies.

Sex-specific social regulation of inflammatory responses and sickness behaviors.

In many mammals, the availability of familiar conspecifics in the home environment can affect immune function and morbidity. Numerous sex differences exist in immune responses, but whether the social environment impacts the immune system differently in males and females is not fully understood. This study examined behavioral and physiological responses to simulated bacterial infection in adult male and female Wistar rats housed either with three same-sex non-siblings (Group) or alone (Isolate). Rats were injected with bacterial lipopolysaccharide (Escherichia coli LPS; 150 microg/kg, i.p.), and behavioral (orectic, locomotor, and social) and physiological (thermoregulatory, cytokine, and corticosterone) inflammatory responses were measured. Among males, LPS-induced fever, suppressed locomotor activity, and inhibited feeding behavior and the magnitude of these responses were greater in Isolate relative to Group housed individuals. In contrast, among females group housing exacerbated behavioral and physiological symptoms of simulated infection. LPS treatments elicited IL-1beta production in all groups, but plasma IL-1beta concentrations were higher and peaked earlier in Isolate relative to Group males, and in Group relative to Isolate females. Furthermore, plasma concentrations of TNFalpha and IL-2 were higher in Group relative to Isolate males. Plasma corticosterone concentrations did not vary as a function of social housing conditions. Together, the data indicate that the social environment markedly influences innate immune responses. Group housing exacerbates inflammatory responses and sickness behaviors in females, but attenuates these responses in males. These sex differences are mediated in part by differential effects of the social environment on pro- and anti-inflammatory cytokine production.

Positive Welfare and the Like: Distinct Views and a Proposed Framework.

Positive welfare and related terms such as good welfare, happiness, and a good life are increasingly used in the animal welfare science literature. Overall, they highlight the welfare benefits of providing animals opportunities for positive experiences, beyond the alleviation of suffering. However, the various terms remain loosely defined and are sometimes used interchangeably, resulting in discrepancy. In this perspective article, we lay out the terms and concepts used in the literature. We identify two distinct views: "hedonic positive welfare," arising from likes and wants and their positive outcomes on welfare; and "positive welfare balance," as an overall positive welfare state based on positive experiences outweighing negative ones. Eudaimonia, satisfaction with one's life, may emerge as a third view. We propose a framework that is applicable across the different views. The "Vienna Framework" outlines different facets: frequency, duration, arousal, context, previous experience, individual differences, sense of agency, and long-term benefit. The framework aims to encourage researchers to consider the relevance of these facets for their own research, to indicate how the facets are affected by different interventions (e.g., greater sense of agency in enriched compared to non-enriched animals), or to compare different topics with respect to the different facets (e.g., high arousal of play behavior and low arousal of social affiliation). We encourage researchers to carefully consider and clearly state how their work falls along these views and facets, conceptually, and operationally. This should prevent dilution of the meaning of positive welfare and thereby preserve its potential to improve the welfare of animals.

Rate of tooth movement under heavy and light continuous orthodontic forces.

INTRODUCTION: The aim of this study was to measure the rate and the amount of orthodontically induced tooth movement under heavy (300 g) and light (50 g) continuous forces with superelastic nickel-titanium closing coils over a defined time (12 weeks). METHODS: Fourteen patients who required maxillary canine retraction into first premolar extraction sites as part of their orthodontic treatment completed this study. In a split-mouth design, precalibrated nickel-titanium closing coil springs delivering a force of 300 g or 50 g were used to distalize the canines after an alignment and stabilization period. Intraoral and maxillary cast measurements were made at the beginning of canine retraction (T0) and every 28 days for 84 days (T1, T2, T3) to assess total space closure, canine retraction rate, canine retraction and molar anchorage loss, and canine rotation. RESULTS: Statistical analysis showed that the amount of initial tooth movement (T0-T1) was not related to force magnitude; however, during the T1-T2 and T2-T3 periods, increased amounts and higher rates of tooth movement were found with heavy forces. These significantly increased the rate and the amount of canine retraction, but the adverse effects of loss of canine rotation control and anchorage were concomitantly increased. Light forces provided a greater percentage of canine retraction than heavy forces, with less strain on anchorage. CONCLUSIONS: Initial tooth movement would benefit from light forces. Heavier forces tend to increase the rate and the amount of canine retraction but lose their advantage because of unwanted clinical side effects.

Oxycodone Exposure: A Magnetic Resonance Imaging Study in Response to Acute and Chronic Oxycodone Treatment in Rats.

The present study was designed to use blood-oxygen-level dependent (BOLD) imaging to "fingerprint" the change in activity in response to oxycodone (OXY) in drug naïve rats before and after repeated exposure to OXY. It was hypothesized that repeated exposure to OXY would initiate adaptive changes in brain organization that would be reflected in an altered response to opioid exposure. Male rats exposed to OXY repeatedly showed conditioned place preference, evidence of drug-seeking behavior and putative neuroadaptation. As these studies were done on awake rats we discovered it was not possible to image rats continuously exposed to OXY due to motion artifact judged to be withdrawal while in the scanner. To circumvent this problem manganese-enhanced MRI (MEMRI) was used to map the distributed integrated activity pattern resulting from continuous OXY exposure. Rats were administered OXY (2.5 mg/kg, i.p.) during image acquisition and changes in BOLD signal intensity were recorded and the activation and deactivation of integrated neural circuits involved in olfaction and motivation were identified. Interestingly, the circuitry of the mesencephalic dopaminergic system showed little activity to the first exposure of OXY. In the MEMRI study, rats received OXY treatments (2.5 mg/kg, twice daily) for four consecutive days following intraventricular MnCl2. Under isoflurane anesthesia, T1-weighted images were acquired and subsequently analyzed showing activity in the forebrain limbic system, ventral striatum, accumbens, amygdala and hippocampus. These results show brain activity is markedly different when OXY is presented to drug naïve rats versus rats with prior, repeated exposure to drug.

Reciprocal affiliation among adolescent rats during a mild group stressor predicts mammary tumors and lifespan.

OBJECTIVE: Although the detrimental physical health effects of social isolation have been known for three decades, the answers to how and why social relationships generally improve health remain elusive. Social relationships are not always beneficial, and we examined a structural dimension that may bring about their salubrious effects: affiliative reciprocity during a stressor. METHODS: In a lifespan study, female rats lived with their sisters and were tested for temperament, affiliative reciprocity during an everyday stressor at puberty, corticosterone response to a stressor, mammary tumor development and diagnosis, and death. RESULTS: Rats that affiliated more reciprocally during a mild group stressor survived longer (p = .0005), having exhibited a lower corticosterone peak in response to an acute novel stressor in late adulthood (p = .0015), and longer time to the development of spontaneous mammary tumors (p = .02). These effects could not be explained solely by the number of affiliative interactions or individual temperament. Indeed, affiliative reciprocity and neophobia were independent and predicted mortality additively (p = .0002). CONCLUSIONS: Affiliative reciprocity during a stressor, a structural quality of social interactions, protected females from early mammary tumor development (the primary pathology in Sprague-Dawley rats) and early all-cause mortality. Conversely, lack of reciprocity (whether disproportionately seeking or receiving attempted affiliation) was as potent a risk factor as neophobia. Thus a social role increased risk additively with individual temperament. Our data indicate that affiliative reciprocity functions as a buffer for everyday stressors and are likely mediated by attenuated reactivity of the hypothalamic-pituitary-adrenal axis.

Olfactory function and the social lives of older adults: a matter of sex.

Social factors play a critical role in a panoply of health processes, including, as recently demonstrated, olfaction. Here, we investigated sex-dependent differences in the relationship between social lives and ability to identify odors in a large sample of nationally representative older US adults (n = 3005, National Social Life and Aging Project (NSHAP)). Social life was measured by the number of friends and close relatives as well as frequency of socializing. We here confirm the association between social lives and olfactory function and extend the notion by showing specifically that olfactory identification ability is modulated by sex in older adults. The connection between olfactory performance and social lives could reflect social modulation of aging as has been reported for health in general. Future studies are necessary to elucidate the precise mechanisms underlying this association and sex difference.

The Serotonin Receptor 6 Antagonist Idalopirdine and Acetylcholinesterase Inhibitor Donepezil Have Synergistic Effects on Brain Activity-A Functional MRI Study in the Awake Rat.

The 5-HT6 receptor is a promising target for cognitive disorders, in particular for Alzheimer's disease (AD) and other CNS disorders. The high-affinity and selective 5-HT6 receptor antagonist idalopirdine (Lu AE58054) is currently in development for mild-moderate AD as adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We studied the effects of idalopirdine alone and in combination with the AChEI donepezil on brain activity using BOLD (Blood Oxygen Level Dependent) functional magnetic resonance imaging (fMRI) in the awake rat. Idalopirdine (2 mg/kg, i.v.) alone had a modest effect on brain activity, resulting in activation of eight brain regions at the peak response. Of these, the cholinergic diagonal band of Broca, the infralimbic cortex, the ventral pallidum, the nucleus accumbens shell, and the magnocellular preoptic area were shared with the effects of donepezil (0.3 mg/kg, i.v.). Donepezil alone activated 19 brain regions at the peak response, including several cortical regions, areas of the septo-hippocampal system and the serotonergic raphe nucleus. When idalopirdine and donepezil were combined, there was a robust stimulation pattern with activation of 36 brain regions spread across the extended-amygdala-, striato-pallidal, and septo-hippocampal networks as well as the cholinergic system. These findings indicate that, whilst idalopirdine and donepezil recruit a number of overlapping regions including one of the forebrain cholinergic nuclei, the synergistic effect of both compounds extends beyond the cholinergic system and the effects of donepezil alone toward recruitment of multiple neural circuits and neurotransmitter systems. These data provide new insight into the mechanisms via which idalopirdine might improve cognition in donepezil-treated AD patients.

Retinal pigment epithelial cells synthesize laminins, including laminin 5, and adhere to them through alpha3- and alpha6-containing integrins.

PURPOSE: Retinal diseases are often accompanied by changes in the structure of the multilayered extracellular matrix underlying the retina, Bruch's membrane (BrM). These structural revisions potentially lead to alterations in retinal pigment epithelium (RPE) adhesion, likely via modification of interactions with extracellular matrix (ECM) proteins including laminins in BrM. The purpose of this study was to identify specific laminins in BrM and their receptors in RPE cells. METHODS: The laminin composition of BrM was determined using biochemical, molecular biological, and immunohistochemical techniques of rat, bovine, and human tissue and cell lines. An adhesion assay was used to test RPE attachment to laminins and the receptors used for this attachment. RESULTS: BrM contained laminin chains that could form laminin heterotrimers including laminins 1, 5, 10, and 11. RPE cells synthesized these laminin chains in vitro. Therefore, RPE cells may synthesize BrM laminins. The RPE cells preferentially adhered to potential BrM laminins. Although the cells adhered to the BrM component collagen IV, these cells preferentially adhered to laminins. Of the laminins tested, the RPE cells adhered preferentially to laminin 5. The cells interacted with these laminins via specific integrins and attained a different morphology on each laminin. In particular, the RPE cells rapidly attached and flattened on laminin 5. CONCLUSIONS: BrM contains specific laminins, and RPE cells express integrin receptors for those laminins. The interaction of these specific laminins and integrins most likely leads to differential behavior of RPE cells.

Non-contact automatic respiration monitoring in restrained rodents.

Prairie voles are socially monogamous rodents that form social bonds similar to those seen in primates. Social behavior investigation in these species, that include studying their breathing regulation, can provide us with an invaluable psychological model to understand social and emotional functions in both animals and humans. There have been several studies associated with the respiratory pattern of these species in the state of fear-induced defense. However, non-invasive measurement methods employed so far suffer from the lack of a natural experiment environment for the rodents. In this paper, we present a remote depth-based system, which applies a modified autocorrelation algorithm to automatically extract respiration patterns in small rodents. We evaluated our estimation accuracy through a series of experiments and comparing the extracted results with breathing rates obtained from visual inspection of synchronously collected RGB videos. In a preliminary test on a human participant, breathing rate was estimated with 100% accuracy, while the estimation accuracy was 94.8% for a restrained vole. Finally, we monitored the respiratory alternations of three voles in transition from a baseline, to a fearful state, and back to a normal state; the estimated breathing rates confirmed the existing hypothesis regarding animal defense strategies.