A bird's eye view of the hippocampus beyond space: Behavioral, neuroanatomical, and neuroendocrine perspectives.

Although the hippocampus is one of the most-studied brain regions in mammals, research on the avian hippocampus has been more limited in scope. It is generally agreed that the hippocampus is an ancient feature of the amniote brain, and therefore homologous between the two lineages. Because birds and mammals are evolutionarily not very closely related, any shared anatomy is likely to be crucial for shared functions of their hippocampi. These functions, in turn, are likely to be essential if they have been conserved for over 300 million years. Therefore, research on the avian hippocampus can help us understand how this brain region evolved and how it has changed over evolutionary time. Further, there is a strong research foundation in birds on hippocampal-supported behaviors such as spatial navigation, food caching, and brood parasitism that scientists can build upon to better understand how hippocampal anatomy, network circuitry, endocrinology, and physiology can help control these behaviors. In this review, we summarize our current understanding of the avian hippocampus in spatial cognition as well as in regulating anxiety, approach-avoidance behavior, and stress responses. Although there are still some questions about the exact number of subdivisions in the avian hippocampus and how that might vary in different avian families, there is intriguing evidence that the avian hippocampus might have complementary functional profiles along the rostral-caudal axis similar to the dorsal-ventral axis of the rodent hippocampus, where the rostral/dorsal hippocampus is more involved in cognitive processes like spatial learning and the caudal/ventral hippocampus regulates emotional states, anxiety, and the stress response. Future research should focus on elucidating the cellular and molecular mechanisms - including endocrinological - in the avian hippocampus that underlie behaviors such as spatial navigation, spatial memory, and anxiety-related behaviors, and in so doing, resolve outstanding questions about avian hippocampal function and organization.

The "seven Deadly Sins" of Neophobia Experimental Design.

Neophobia, an aversive response to novelty, is a behavior with critical ecological and evolutionary relevance for wild populations because it directly influences animals' ability to adapt to new environments and exploit novel resources. Neophobia has been described in a wide variety of different animal species from arachnids to zebra finches. Because of this widespread prevalence and ecological importance, the number of neophobia studies has continued to increase over time. However, many neophobia studies (as well as many animal behavior studies more generally) suffer from one or more of what we have deemed the "seven deadly sins" of neophobia experimental design. These "sins" include: 1) animals that are not habituated to the testing environment, 2) problems with novel stimulus selection, 3) non standardized motivation, 4) pseudoreplication, 5) lack of sufficient controls, 6) fixed treatment order, and 7) using arbitrary thresholds for data analysis. We discuss each of these potential issues in turn and make recommendations for how to avoid them in future behavior research. More consistency in how neophobia studies are designed would facilitate comparisons across different populations and species and allow researchers to better understand whether neophobia can help explain animals' responses to human-altered landscapes and the ability to survive in the Anthropocene.

Effect of estradiol and predator cues on behavior and brain responses of captive female house sparrows (Passer domesticus).

The presence of predators can cause major changes in animal behavior, but how this interacts with hormonal state and brain activity is poorly understood. We gave female house sparrows (Passer domesticus) in post-molt condition an estradiol (n = 17) or empty implant (n = 16) for 1 week. Four weeks after implant removal, a time when female sparrows show large differences in neuronal activity to conspecific vs. heterospecific song, we exposed birds to either 30 min of conspecific song or predator calls, and video recorded their behavior. Females were then euthanized, and we examined neuronal activity using the expression of the immediate early gene (IEG) ZENK to identify how the acoustic stimuli affected neuronal activation. We predicted that if female sparrows with estradiol implants reduce neuronal activity in response to predator calls as they do to neutral tones and non-predatory heterospecifics, they would show less fear behavior and a decreased ZENK response in brain regions involved in auditory (e.g., caudomedial mesopallium) and threat perception functions (e.g., medial ventral arcopallium) compared to controls. Conversely, we predicted that if females maintain auditory and/or brain sensitivity towards predator calls, then female sparrows exposed to estradiol would not show any differences in ZENK response regardless of playback type. We found that female sparrows were less active during predator playbacks independent of hormone treatment and spent more time feeding during conspecific playback if they had previously been exposed to estradiol. We observed no effect of hormone or sound treatment on ZENK response in any region of interest. Our results suggest that female songbirds maintain vigilance towards predators even when in breeding condition.

Exploration of A novel environment is not correlated with object neophobia in wild-caught house sparrows (Passer domesticus).

Novel object, food, and environment trials have been widely used to understand how individual variation in neophobia (an aversion to novelty) relates to variation in endocrine, physiological, and ecological traits. However, what is often missing from these studies is an evaluation of whether an animal's response to one type of neophobia test is reflective of its response to other neophobia tests. In this study we investigated whether spatial neophobia was significantly correlated with responses to a novel object paradigm. In spatial neophobia trials, wild-caught house sparrows (n = 23) were allowed access to a novel environment (an adjacent cage with familiar objects placed in new locations). Time to first enter and total time spent in the novel environment were assessed. In novel object trials, birds were exposed to a new novel object in, on, or near their food dish and time to approach and feed from the dish was measured. Results indicate that neither time spent in a novel environment nor time to first enter a novel environment were correlated with an individual's average response to novel object trials. Therefore, these two tests may be assessing two discrete behaviors that involve separate decision-making processes and functional circuits in the brain.

Handling and restraint induce a significant increase in plasma corticosterone in Hispaniolan Amazon parrots (Amazona ventralis).

OBJECTIVE: To measure baseline plasma corticosterone levels in Hispaniolan Amazon parrots (Amazona ventralis) and assess the effects of handling and restraint on corticosterone levels over 1 hour, reflective of what parrots might experience during veterinary care. ANIMALS: 10 male and 12 female Hispaniolan Amazon parrots. PROCEDURES: Each parrot was removed from its cage and wrapped in a towel for restraint similar to that performed in a clinical setting. An initial baseline blood sample was collected in < 3 minutes upon entrance into the parrot room, after which blood samples were taken every 15 minutes for 1 hour (a total of 5 blood samples). An enzyme-linked immunoassay was validated for Hispaniolan Amazon parrots and used to determine concentrations of plasma corticosterone. RESULTS: On average, parrots showed a significant increase in corticosterone between baseline samples and all subsequent postrestraint time points (average baseline corticosterone ± SD: 0.51 ± 0.65 ng/mL). Females, on average, displayed significantly higher corticosterone levels than males after 30, 45, and 60 minutes of restraint (P = .016, P = .0099, and P = .015, respectively). Birds with feather-destructive behavior did not have significantly higher corticosterone levels than birds without the condition (P = .38). CLINICAL RELEVANCE: Understanding the physiological stress response in companion psittacine birds during routine handling will allow clinicians to better evaluate how this may affect the patient's condition and diagnostic test results. Assessing how corticosterone correlates to behavioral conditions such as feather-destructive behavior will provide clinicians with the potential to develop treatment options.

Optimized Methodology for Reference Region and Image-Derived Input Function Kinetic Modeling in Preclinical PET.

PET imaging of small animals is often used for assessing biodistribution of a novel radioligand and pharmacology in small animal models of disease. PET acquisition and processing settings may affect reference region or image-derived input function (IDIF) kinetic modeling estimates. We examined four different factors in comparing quantitative results: 1) effect of reconstruction algorithm, 2) number of MAP iterations, 3) strength of the MAP prior, and 4) Attenuation and scatter. The effect of these parameters has not been explored for small-animal reference region and IDIF kinetic modeling approaches. Dynamic PET/CT scans were performed in 3 species with 3 different tracers: house sparrows with [11C]raclopride, rats with [18F]AS2471907 (11ßHSD1) and mice with [11C]UCB-J (SV2A). FBP yielded lower kinetic modeling estimates compared to 3D-OSEM-MAP reconstructions, in sparrow and rat studies. Target resolutions (MAP prior strength) of 1.5 and 3.0mm demonstrated reduced VT in rats but only 3.0mm reduced BP ND in sparrows. Therefore, use of the highest target resolution (0.8mm) is warranted. We demonstrated using kinetic modeling that forgoing CT-based attenuation and scatter correction may be appropriate to improve animal throughput when using short-lived radioisotopes in sparrows and mice. This work provides recommendations and a framework for future optimization of kinetic modeling for preclinical PET methodology with novel radioligands.

Constitutive gene expression differs in three brain regions important for cognition in neophobic and non-neophobic house sparrows (Passer domesticus).

Neophobia (aversion to new objects, food, and environments) is a personality trait that affects the ability of wildlife to adapt to new challenges and opportunities. Despite the ubiquity and importance of this trait, the molecular mechanisms underlying repeatable individual differences in neophobia in wild animals are poorly understood. We evaluated wild-caught house sparrows (Passer domesticus) for neophobia in the lab using novel object tests. We then selected a subset of neophobic and non-neophobic individuals (n = 3 of each, all females) and extracted RNA from four brain regions involved in learning, memory, threat perception, and executive function: striatum, caudal dorsomedial hippocampus, medial ventral arcopallium, and caudolateral nidopallium (NCL). Our analysis of differentially expressed genes (DEGs) used 11,889 gene regions annotated in the house sparrow reference genome for which we had an average of 25.7 million mapped reads/sample. PERMANOVA identified significant effects of brain region, phenotype (neophobic vs. non-neophobic), and a brain region by phenotype interaction. Comparing neophobic and non-neophobic birds revealed constitutive differences in DEGs in three of the four brain regions examined: hippocampus (12% of the transcriptome significantly differentially expressed), striatum (4%) and NCL (3%). DEGs included important known neuroendocrine mediators of learning, memory, executive function, and anxiety behavior, including serotonin receptor 5A, dopamine receptors 1, 2 and 5 (downregulated in neophobic birds), and estrogen receptor beta (upregulated in neophobic birds). These results suggest that some of the behavioral differences between phenotypes may be due to underlying gene expression differences in the brain. The large number of DEGs in neophobic and non-neophobic birds also implies that there are major differences in neural function between the two phenotypes that could affect a wide variety of behavioral traits beyond neophobia.

Novel objects alter immediate early gene expression globally for ZENK and regionally for c-Fos in neophobic and non-neophobic house sparrows.

Neophobia - an animal's reluctance to approach novel objects, try new foods, or explore unfamiliar environments - affects whether animals can adapt to new environments and exploit novel resources. However, despite its importance, the neurobiological mechanisms underlying this personality trait are poorly understood. In this study, we examined regional brain activity using the expression of two immediate early genes (IEGs), ZENK and c-Fos, in response to novel objects or control conditions in captive house sparrows (Passer domesticus, n = 22). When exposed to novel objects, we predicted that we would see differential IEG activity in brain regions involved in regulating stress and emotion (hippocampus, medial ventral arcopallium, lateral septum), reward and learning (striatum), and executive function (NCL) between neophobic and non-neophobic individuals. To classify birds by phenotype, we used behavior trials that tested willingness to approach a food dish in the presence of several different novel objects, habituation to one novel object, and willingness to try several different novel foods. We then exposed birds to a new novel object or a control condition and assessed protein expression of two IEGs in neophobic vs non-neophobic individuals after this final exposure. An analysis of average sparrow feeding times in the presence of novel objects showed a bimodal distribution of neophobia behavior. There was also high repeatability of individual novel object responses, and average responses to all three trial types (novel object, novel food, and habituation to a novel object) were significantly correlated. Although we saw no differences between neophobic and non-neophobic birds in IEG expression in response to novel objects in any of the 6 brain regions examined, there was a significant global decrease in ZENK expression and a significant increase in c-Fos expression in the medial ventral arcopallium and the caudal hippocampus in response to novel objects compared to controls, suggesting that these two regions may be important in novelty detection and threat perception. Additionally, there was no object effect in the rostral hippocampus, which supports the hypothesis that the avian hippocampus may have a rostrocaudal functional gradient similar to the septotemporal gradient in mammals.

Chronic stress and captivity alter the cloacal microbiome of a wild songbird.

There are complex interactions between an organism's microbiome and its response to stressors, often referred to as the 'gut-brain axis'; however, the ecological relevance of this axis in wild animals remains poorly understood. Here, we used a chronic mild stress protocol to induce stress in wild-caught house sparrows (Passer domesticus), and compared microbial communities among stressed animals, those recovering from stress, captive controls (unstressed) and a group not brought into captivity. We assessed changes in microbial communities and abundance of shed microbes by culturing cloacal samples on multiple media to select for aerobic and anaerobic bacteria and fungi. We complemented this with cultivation-independent 16S and ITS rRNA gene amplification and sequencing, pairing these results with host physiological and immune metrics, including body mass change, relative spleen mass and plasma corticosterone concentrations. We found significant effects of stress and captivity on the house sparrow microbiomes, with stress leading to an increased relative abundance of endotoxin-producing bacteria - a possible mechanism for the hyperinflammatory response observed in captive avians. While we found evidence that the microbiome community partially recovers after stress cessation, animals may lose key taxa, and the abundance of endotoxin-producing bacteria persists. Our results suggest an overall link between chronic stress, host immune system and the microbiome, with the loss of potentially beneficial taxa (e.g. lactic acid bacteria), and an increase in endotoxin-producing bacteria due to stress and captivity. Ultimately, consideration of the host's microbiome may be useful when evaluating the impact of stressors on individual and population health.

A transient reduction in circulating corticosterone reduces object neophobia in male house sparrows.

Aversive reactions to novelty (or "neophobia") have been described in a wide variety of different animal species and can affect an individual's ability to exploit new resources and avoid potential dangers. However, despite its ecological importance, the proximate causes of neophobia are poorly understood. In this study, we tested the role of glucocorticoid hormones in neophobia in wild-caught house sparrows (Passer domesticus, n = 11 males) by giving an injection of the drug mitotane that reduced endogenous corticosterone for several days or a vehicle control, and then examined the latency to feed when the food dish was presented with or without a novel object in, on, or near the dish. Each sparrow was exposed to multiple novel object and control trials and received both vehicle control and mitotane treatments, with a week between treatments to allow the drug to wash out. As found previously, all novel objects significantly increased sparrows' latency to feed compared to no object present. Reducing corticosterone using mitotane significantly reduced the latency to feed in the presence of novel objects. In control trials without objects, mitotane had no significant effects on feeding time. Although we have shown that corticosterone affects neophobia, further studies using specific receptor agonists and antagonists will help clarify the neurobiological mechanisms involved and determine whether baseline or stress-induced corticosterone is driving this effect. These results suggest that increased glucocorticoids (e.g., due to human-induced stressors) could increase neophobia, affecting the ability of individuals to exploit novel resources, and, ultimately, to persist in human-altered environments.

Glucocorticoid negative feedback as a potential mediator of trade-offs between reproduction and survival.

A large increase in glucocorticoid hormones can inhibit or completely shut down breeding in wild animals. Because of its critical role in reducing glucocorticoids after exposure to stressors, hypothalamic-pituitary-adrenal (HPA) negative feedback could be an important mediator of the ecological trade-off between investing limited resources into survival/self vs. reproduction/offspring. Although assessing negative feedback in a standardized way using injections of the synthetic glucocorticoid dexamethasone is a straightforward procedure, we show that several different approaches are used to report negative feedback in the literature, and then demonstrate that this can in turn affect the statistical results and conclusions of a study. We then review six specific predictions about adaptive within- and across-species patterns in glucocorticoids based on the relative costs and benefits of maintaining or abandoning breeding attempts when animals are faced with prolonged strong stressors, and examine evidence for these predictions in the context of HPA negative feedback. Thus far, evidence supporting these predictions for negative feedback is mixed, with the strongest evidence supporting a link between poor body condition and weak negative feedback in breeding animals. However, more research is necessary to assess the importance of changes in HPA negative feedback, especially in reptile, fish, and amphibian species. Furthermore, future research would benefit from reporting negative feedback ability in a standardized way, or at least making raw data available for the computation of alternate measures, to more easily compare studies in this growing area of research.

In vivo imaging of D2 receptors and corticosteroids predict behavioural responses to captivity stress in a wild bird.

Individual physiological variation may underlie individual differences in behaviour in response to stressors. This study tested the hypothesis that individual variation in dopamine and corticosteroid physiology in wild house sparrows (Passer domesticus, n = 15) would significantly predict behaviour and weight loss in response to a long-term stressor, captivity. We found that individuals that coped better with captivity (fewer anxiety-related behaviours, more time spent feeding, higher body mass) had lower baseline and higher stress-induced corticosteroid titres at capture. Birds with higher striatal D2 receptor binding (examined using positron emission tomography (PET) with 11C-raclopride 24 h post-capture) spent more time feeding in captivity, but weighed less, than birds with lower D2 receptor binding. In the subset of individuals imaged a second time, D2 receptor binding decreased in captivity in moulting birds, and larger D2 decreases were associated with increased anxiety behaviours 2 and 4 weeks post-capture. This suggests changes in dopaminergic systems could be one physiological mechanism underlying negative behavioural effects of chronic stress. Non-invasive technologies like PET have the potential to transform our understanding of links between individual variation in physiology and behaviour and elucidate which neuroendocrine phenotypes predict stress resilience, a question with important implications for both humans and wildlife.

Host sex, size, and hemoparasite infection influence the effects of ectoparasitic burdens on free-ranging iguanas.

Investigations focusing on host-ectoparasite interactions in animals have revealed asymptomatic to severe health and fitness consequences suggesting that species mobilize different interspecific response mechanisms. Fewer studies, however, have examined intraspecific responses to ectoparasitic burdens. In this study, we analyzed host health and fitness responses to increasing ectoparasite burdens along with the presence/absence of hemoparasites of free-ranging insular rock iguanas (Cyclura cychlura) in The Bahamas. Using hematology, plasma biochemistry, as well as body condition and growth rate comparisons, we failed to find significant associations of tick burdens with annual growth rate, corticosterone, packed cell volume, total white blood cell, and heterophil, monocyte, eosinophil or hemoglobin measures. We did, however, find mixed and significant associations of tick burdens with lymphocyte and basophil counts, heterophil-to-lymphocyte ratios, and body condition indices. These associations varied by sex, size, and hemoparasite infection status suggesting that different life stages of iguanas may invest differently in immune responses, and impacts may be modulated based on size and sex of hosts, and coinfection status.

A 3D-printed modular device for imaging the brain of small birds.

BACKGROUND: One potential barrier to using in vivo imaging in any new animal species is solving the basic problem of how to hold animals safely and securely during scans. NEW METHOD: In this paper, we describe the design, fabrication, use, and positional reproducibility of a 3D-printed plastic device (the Avian Imaging Device, or AID) for imaging the brain of 1 or 2 small songbirds. We designed two different types of head cones to use with this device: one that was not contoured and designed for anesthesia induction, and one contoured to the shape of a house sparrow head, designed to be used with a pre-anesthetized animal. RESULTS: Compared to no holder, using the AID with both contoured and non-contoured head cones significantly reduced the amount of translation necessary to align the head in pairs of CT scans (by 78% and 90%, respectively); using the contoured head cone also significantly reduced the amount of rotation necessary for head alignment in registering pairs of scans (by 90%). COMPARISON WITH EXISTING METHOD(S): Using an animal holder that can not only securely hold animals but which has high positional reproducibility is essential to take advantage of the maximum resolution possible with small animal imaging. 3D-printed materials are also compatible with PET and CT, environmentally stable, and fast and inexpensive to make. CONCLUSIONS: Researchers can learn from the design of the AID and use our CAD models as a starting point for fabricating devices for multiple small-animal imaging needs.

Estradiol modulates neural response to conspecific and heterospecific song in female house sparrows: An in vivo positron emission tomography study.

Although there is growing evidence that estradiol modulates female perception of male sexual signals, relatively little research has focused on female auditory processing. We used in vivo 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging to examine the neuronal effects of estradiol and conspecific song in female house sparrows (Passer domesticus). We assessed brain glucose metabolism, a measure of neuronal activity, in females with empty implants, estradiol implants, and empty implants ~1 month after estradiol implant removal. Females were exposed to conspecific or heterospecific songs immediately prior to imaging. The activity of brain regions involved in auditory perception did not differ between females with empty implants exposed to conspecific vs. heterospecific song, but neuronal activity was significantly reduced in females with estradiol implants exposed to heterospecific song. Furthermore, our within-individual design revealed that changes in brain activity due to high estradiol were actually greater several weeks after peak hormone exposure. Overall, this study demonstrates that PET imaging is a powerful tool for assessing large-scale changes in brain activity in living songbirds, and suggests that after breeding is done, specific environmental and physiological cues are necessary for estradiol-stimulated females to lose the selectivity they display in neural response to conspecific song.

Experimentally reducing corticosterone mitigates rapid captivity effects on behavior, but not body composition, in a wild bird.

Wild animals and captives display physiological and behavioral differences, and it has been hypothesized, but rarely tested, that these differences are caused by sustained elevation of the hormone corticosterone. We used repeated computed tomography (CT) imaging to examine body composition changes in breeding male and female wild house sparrows (Passer domesticus; n=20) in response to two weeks of captivity, and assessed behavioral changes using video recordings. Half of the birds received the drug mitotane, which significantly decreased stress-induced corticosterone titers compared to controls. Based on the CT images, fat volumes increased, and pectoralis muscle density and heart and testes volumes decreased, over the two weeks of captivity in both groups of birds. However, beak-wiping, a behavior that can indicate anxiety and aggression, showed increased occurrence in controls compared to mitotane-treated birds. While our results do not support the hypothesis that these body composition changes were primarily driven by stress-induced corticosterone, our data suggest that experimentally reducing stress-induced corticosterone may mitigate some captivity-induced behavioral changes. Broadly, our results emphasize that researchers should take behavioral and physiological differences between free-living animals and captives into consideration when designing studies and interpreting results. Further, time in captivity should be minimized when birds will be reintroduced back to the wild.

Does corticosterone regulate the onset of breeding in free-living birds?: The CORT-Flexibility Hypothesis and six potential mechanisms for priming corticosteroid function.

For many avian species, the decision to initiate breeding is based on information from a variety of environmental cues, including photoperiod, temperature, food availability, and social interactions. There is evidence that the hormone corticosterone may be involved in delaying the onset of breeding in cases where supplemental cues, such as low food availability and inclement weather, indicate that the environment is not suitable. However, not all studies have found the expected relationships between breeding delays and corticosterone titers. In this review, we present the hypothesis that corticosterone physiology mediates flexibility in breeding initiation (the "CORT-Flexibility Hypothesis"), and propose six possible corticosterone-driven mechanisms in pre-breeding birds that may delay breeding initiation: altering hormone titers, negative feedback regulation, plasma binding globulin concentrations, intracellular receptor concentrations, enzyme activity and interacting hormone systems. Based on the length of the breeding season and species-specific natural history, we also predict variation in corticosterone-regulated pre-breeding flexibility. Although few studies thus far have examined mechanisms beyond plasma hormone titers, the CORT-Flexibility Hypothesis is grounded on a solid foundation of research showing seasonal variation in the physiological stress response and knowledge of physiological mechanisms modulating corticosteroid effects. We propose six possible mechanisms as testable and falsifiable predictions to help clarify the extent of HPA axis regulation of the initiation of breeding.

Wounding alters blood chemistry parameters and skin mineralocorticoid receptors in house sparrows (Passer domesticus).

Because skin is an important physical barrier against pathogens, the ability to quickly and effectively heal wounds directly impacts an animal's health. The hormone corticosterone (CORT) has many complex effects on immune function and can slow wound healing. It has been suggested that CORT's role during wound healing may be to act as a "brake" on inflammation and cell proliferation. This project aimed to clarify the role of CORT in the healing process by quantifying concentrations of its two intracellular receptors, glucocorticoid receptors (GR) and mineralocorticoid receptors (MR), in the skin of wounded (n = 9) or unwounded (n = 8) house sparrows (Passer domesticus) using radioligand binding assays. We also quantified GR and MR in liver, spleen and pectoralis muscle, as well as several blood chemistry parameters, hypothesizing that wounding would alter whole-body energy use. One day post-wounding, wounded birds had higher blood glucose and lower aspartate aminotransferase (a marker indicating muscle damage or catabolism) compared to controls, which may be related to animals' changing metabolic needs in response to lymphocyte and macrophage recruitment at the wound site. Birds had significantly decreased MR, but not GR, in the skin of wounded legs compared to the skin of unwounded legs. There was also a trend towards lower MR in wounded skin compared to unwounded birds. Receptors in the three other tissues did not differ between groups. This study suggests that decreasing the skin's sensitivity to CORT immediately after wounding may be a necessary part of the normal healing process in wild birds.

Are receptor concentrations correlated across tissues within individuals? A case study examining glucocorticoid and mineralocorticoid receptor binding.

Hormone receptors are a necessary (although not sufficient) part of the process through which hormones like corticosterone create physiological responses. However, it is currently unknown to what extent receptor concentrations across different target tissues may be correlated within individual animals. In this study, we examined this question using a large dataset of radioligand binding data for glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in 13 different tissues in the house sparrow (Passer domesticus) (n=72). Our data revealed that individual house sparrows tended to exhibit higher or lower receptor binding across all tissues, which could be part of what creates the physiological and behavioral syndromes associated with different hormonal profiles. However, although statistically significant, the correlations between tissues were very weak. Thus, when each tissue was independently regressed on receptor concentrations in the other tissues, multivariate analysis revealed significant relationships only for sc fat (for GR) and whole brain, hippocampus, kidney, omental fat, and sc fat (for MR). We also found significant pairwise correlations only between receptor concentrations in brain and hippocampus, and brain and kidney (both for MR). This research reveals that although there are generalized individual consistencies in GR and MR concentrations, possibly due to such factors as hormonal regulation and genetic effects, the ability of 2 different tissues to respond to the same hormonal signal appears to be affected by additional factors that remain to be identified.

Seasonal variation in glucocorticoid and mineralocorticoid receptors in metabolic tissues of the house sparrow (Passer domesticus).

Glucocorticoid hormones like corticosterone (CORT) play essential metabolic roles at both baseline and stress-induced concentrations, and CORT titers vary seasonally in patterns occurring across many different vertebrate species. It has been hypothesized that CORT may vary seasonally due to changing energy requirements at different times of year. However, hormone effects are dependent on binding to receptors in target tissues, and receptors might also vary seasonally. CORT alters metabolism primarily through binding to two receptors, the high-affinity mineralocorticoid receptor (MR) and low-affinity glucocorticoid receptor (GR). We quantified GR and MR in metabolic tissues (liver, kidney, omental and subcutaneous fat, and gastrocnemius and pectoralis muscle) of wild-caught house sparrows (Passer domesticus) to assess these tissues' capacity to respond to CORT-mediated metabolic demands. We quantified receptors using radioligand binding assays in early and late winter, pre-egg-laying, breeding, late breeding and molt (n=12 at each stage). MR binding did not vary significantly in any tissue over the course of the year. Because MR is associated with baseline CORT effects, this suggests that changing hormone titers may primarily regulate baseline CORT effects on metabolism. Seasonal modulation of GR binding occurred in every tissue but omental fat, though peak receptor density did not coincide with peak stress-induced CORT concentrations measured previously. Because GR is associated with stress-induced CORT effects, these data demonstrate seasonal patterns in stress-induced CORT are not driven by metabolic needs alone, although at different times of year sparrows may vary which tissue types respond to increased energy demands resulting from exposure to stressors.