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The prenatal period can shape adult phenotype. Appetite is governed by the melanocortin system and regulated by neuroendocrine mechanisms that are vulnerable to stress. By investigating the neurobiological mechanisms of early life stress programming on hypothalamic feeding circuits we aimed to determine appetite development in birds and the impact of pre-natal stress. We investigated how changes in nutritional status, food availability, and early life stress programming effect the hypothalamic appetite pathways in Japanese quail (Coturnix japonica). Nine-day old female and male chicks (19L:5D), were randomly assigned to FED (control, ad libitum feeding) or FASTED (food removed at lights off and 4h fast from lights on) and FED CORT (ad libitum feeding, in ovo corticosterone injection at incubation day 5) groups. FASTED chicks had lower body and gut weights and lower blood glucose compared to FED control or FED CORT; no sex differences were observed. Behavioural analysis of video recordings showed that FED, FED CORT and FASTED chicks rested and rarely fed or drank during darkness. Following lights on, all chicks exhibited food-seeking behaviour (increased visits to feeding station during the first 2h of lights on), with more food seeking behaviour in FASTED chicks compared to FED and FED CORT chicks. RT-qPCR showed increased hypothalamic neuropeptide-Y (NPY) mRNA expression in FASTED compared to FED and FED CORT chicks. There were no differences in agouti-related peptide (AgRP), or proopiomelanocortin (POMC) and no differences in NPY, AgRP and POMC mRNA between FED control and FED CORT groups. These findings suggest that there are some functional differences in the neuropeptide mechanisms regulating food intake in young birds compared to adults and that early life stress does not alter feeding related neuropeptides in young quail.All work was performed under UK Home Office licence, ARRIVE guidelines and ethical review. Research supported by BBSRC (BB/5015760/1).

Extreme weather events are becoming more frequent because of climate change. Understanding how organisms respond to adverse environmental conditions is a prerequisite to coping with environmental challenges. We studied a unique set of samples collected from free-living Lapland longspurs (Calcarius laponnicus) during their arrival and incubation. Birds were sampled at an extreme arrival period, a typical arrival period, and incubation before and during a severe snowstorm. To understand how climate change influences the biological systems of wild birds, we performed RNA-seq on the liver, hypothalamus, heart, and gonad. Plasma levels of glucocorticoids were elevated in response to stress handling during the extreme spring and during the snowstorm. We identified storm-associated differentially expressed genes (DEGs). In particular, the gene encoding FKBP5 was up-significantly regulated in hypothalamus, suggesting that FKBP5 is functionally important for the response to inclement weather. FKBP5 is a regulator of the Hypothalamic-Pituitary-Adrenal (HPA) axis stress-response, and it acts to modulate glucocorticoid receptor sensitivity. FKBP5 acts as a co-chaperone, negatively regulating the glucocorticoid signalling pathway and provides a mechanism by which an individual can adjust to environmental perturbations. Such findings will build on our understanding of endocrine mediated stress and resilience in freely living animals in a changing world. Extreme weather events are becoming more frequent because of climate change. Understanding how organisms respond to adverse environmental conditions is a prerequisite to coping with environmental challenges. Wild animals are an excellent proxy, so we studied a unique set of samples collected from wild Lapland longspur (Calcarius laponnicus) breeding in Alaska, representing different tissues under exposure to different environmental conditions, including a severe snowstorm. To understand how climate change influences the biological systems of wild birds, we performed RNA-seq on different tissues including liver, hypothalamus, heart, and gonad, with the presence and absence of storm condition.We identified many storm-associated differentially expressed genes (DEGs). In particular, when comparing the differentially expressed genes in hypothalamus, the gene encoding FKBP5 is significantly up-regulated, which suggests FKBP5 is functionally important in response to storm conditions. FKBP5 is a regulator of the Hypothalamic-Pituitary-Adrenal axis and stress-response, and in response to stress FKBP5 modulates glucocorticoid receptor sensitivity. FKBP5 acts as a co-chaperone, negatively regulating the glucocorticoid signalling pathway and other biological functions. Such findings will provide the foundations to develop resilience strategies to mitigate potentially devastating effects in all life on earth including those of global agricultural importance.

The regulation of feeding is a complex interaction between central and peripheral signalling governed centrally by the melanocortin system comprising specific neuronal populations and circuits in the hypothalamus and brainstem. Little is known about the central mechanisms regulating the onset of appetite in birds in early life and here we investigated how changes in nutritional status and food availability effect the hypothalamic pathways modulating appetite in young Japanese quail (Coturnix japonica). Nine-day old female and male chicks housed on 19L:5D, were randomly assigned to FED (control, ad libitum feeding) or FASTED (food removed at lights off and 4 hour fast from lights on) groups. FASTED chicks exhibited significantly lower body and gut weights as well as lower blood glucose levels compared to FED controls and no sex differences were observed. FASTED chicks also displayed more depolarised resting membrane potentials resulting in higher rates of spontaneous action potential firing in arcuate nucleus neurones using patch clamp electrophysiology. RFID PIT tag data and behavioural analysis of video recordings showed that FED and FASTED chicks rested and rarely fed or drank during darkness. Following lights on all chicks immediately exhibited food-seeking behaviour and the feeding station was visited with increased frequency during the first 2h of lights on; FASTED chicks showed more food seeking behaviour compared to FED chicks. RT-qPCR analysis showed increased hypothalamic mRNA expression for neuropeptideY (NPY), but not its receptor (NPYR1 or NPYR2), agouti-related peptide (AgRP), proopiomelanocortin (POMC), cocaine-and-amphetamine-regulated transcript (CART), gonadotrophin inhibitory hormone (GnIH) or its receptor (GnIHR, GPR147) in FASTED chicks. Despite conserved peptide signalling among vertebrates, these findings suggest that there are some functional differences in the neuropeptide mechanisms regulating food intake in birds compared to mammals

Cognitive traits are predicted to be under intense selection in animals moving into new environments and may determine the success, or otherwise, of dispersal and invasions. In particular, spatial information related to resource distribution is an important determinant of neural development. Spatial information is predicted to vary for invasive species encountering novel environments. However, few studies have tested how cognition or neural development varies intraspecifically within an invasive species. In Australia, the non-native common starling Sturnus vulgaris inhabits a range of habitats that vary in seasonal resource availability and distribution. We aimed to identify variations in the brain mass and hippocampus volume of starlings in Australia related to environmental variation across two substantially different habitat types. Specifically, we predicted variation in brain mass and hippocampal volume in relation to environmental conditions, latitude, and climatic variables. To test this, brain mass and volumes of the hippocampus and two control brain regions (telencephalon and tractus septomesencephalicus) were quantified from starling brains gathered from across the species' range in south eastern Australia. When comparing across an environmental gradient, there was a significant interaction between sex and environment for overall brain mass, with greater sexual dimorphism in brain mass in inland populations compared to those at the coast. There was no significant difference in hippocampal volume in relation to environmental measures (hippocampus volume, n = 17) for either sex. While these data provide no evidence for intraspecific environmental drivers for changes in hippocampus volume in European starlings in Australia, they do suggest that environmental factors contribute to sex differences in brain mass. This study identifies associations between the brain volume of a non-native species and the environment; further work in this area is required to elucidate the mechanisms driving this relationship.

Lesch-Nyhan disease (LND) is a severe neurological disorder caused by loss-of-function mutations in the gene encoding hypoxanthine phosphoribosyltransferase (HPRT), an enzyme required for efficient recycling of purine nucleotides. Although this biochemical defect reconfigures purine metabolism and leads to elevated levels of the breakdown product urea, it remains unclear exactly how loss of HPRT activity disrupts brain function. As the rat is the preferred rodent experimental model for studying neurobiology and diseases of the brain, we used genetically-modified embryonic stem cells to generate an HPRT knock-out rat. Male HPRT-deficient rats were viable, fertile and displayed normal caged behaviour. However, metabolomic analysis revealed changes in brain biochemistry consistent with disruption of purine recycling and nucleotide metabolism. Broader changes in brain biochemistry were also indicated by increased levels of the core metabolite citrate and reduced levels of lipids and fatty acids. Targeted MS/MS analysis identified reduced levels of dopamine in the brains of HPRT-deficient animals, consistent with deficits noted previously in human LND patients and HPRT knock-out mice. The HPRT-deficient rat therefore provides a new experimental platform for future investigation of how HPRT activity and disruption of purine metabolism affects neural function and behaviour.

The acute stress response in vertebrates is a highly adaptive suite of physiological and behavioural mechanisms that promote survival in the face of deleterious stimuli from the environment. Facultative changes of physiology and behaviour are mediated through changes in circulating levels of glucocorticoids (corticosterone, cortisol) and their subsequent binding to the high affinity mineralocorticoid receptor (MR) or the low affinity glucocorticoid receptor (GR). Free-living wild Gambel's White-crowned sparrows (Zonotrichia leucophrys gambelii) display annual fluctuations in the stress response with marked attenuation during the transition from the pre-parental to the parental stage. We investigated whether this rapid reduction in the stress response is mediated through changes in MR and GR mRNA expression in the brain using in situ hybridisation. MR mRNA expression was significantly lower in the hippocampus as the birds became parental. No changes were observed in GR mRNA expression in the paraventricular nucleus (PVN) or preoptic area (POA) at this time. No significant correlations were found between initial capture levels of corticosterone and GR or MR mRNA expression. No differences were found in basal levels of corticosterone between pre-parental and parental in birds collected for in situ hybridisation. Stress response data revealed no difference at baseline but reductions in peak levels of corticosterone as birds became parental. These data suggest that changes in MR expression may be important for the regulation of the stress response or behavioural stress sensitivity in order to promote parental care and investment.

The anterior olfactory nucleus (AON), a component of the main olfactory system, is a cortical region that processes olfactory information and acts as a relay between the main olfactory bulbs and higher brain regions such as the piriform cortex. Utilizing a transgenic rat in which an enhanced green fluorescent protein reporter gene is expressed in vasopressin neurones (eGFP-vasopressin), we have discovered a population of vasopressin neurones in the AON. These vasopressin neurones co-express vasopressin V1 receptors. They also co-express GABA and calbinin-D28k indicating that they are neurochemically different from the newly described vasopressin neurons in the main olfactory bulb. We utilized the immediate early gene product, early growth response protein 1 (Egr-1), to examine the functional role of these vasopressin neurons in processing social and non-social odours in the AON. Exposure of adult rats to a conspecific juvenile or a heterospecific predator odour leads to increases in Egr-1 expression in the AON in a subregion specific manner. However, only exposure to a juvenile increases Egr-1 expression in AON vasopressin neurons. These data suggest that vasopressin neurones in the AON may be selectively involved in the coding of social odour information.