Neural Circuits Underlying Nest Building in Male Zebra Finches.

Nest building consists of a series of motor actions, which are concomitant with activity in regions of the anterior motor pathway, the social behavior network, and the reward circuity in nest building adult male zebra finches (Taeniopygia guttata). It is not clear, however, whether this activity is due to nest building, collection, and/or manipulation of nest material. To identify which areas of the brain are specifically involved, we used immunohistochemistry to quantify the immediate early gene c-Fos in male zebra finches that were nest building (Building), birds given a nest box but could interact only with tied down nest material (Fixed), and birds that were not given a nest box or nest material (Control). We investigated the following brain regions: the anterior motor pathway (anterior ventral mesopallium [AMV], AN, anterior striatum [ASt]), areas of the social behavior network (bed nucleus of the stria terminalis, dorsomedial subdivision [BSTmd], lateral septum [LS]), the dopaminergic reward circuitry (ventral tegmental area), and the cerebellum. We found that there was greater Fos immunoreactivity expression in the BSTmd, LS, and AMV with increased material deposition; in LS, AMV ASt, and Folium VI with increased material carrying; in LS, AMV, and ASt with increased nest material tucking; and in LS and all folia (except Folium VIII) with increased tugging at tied down material. These data confirm a functional role for areas of the anterior motor pathway, social behavior network, and the cerebellum in nest material collection and manipulation by birds.

Using Teleost Fish to Discern Developmental Signatures of Evolutionary Adaptation From Phenotypic Plasticity in Brain Structure.

Traditionally, the impact of evolution on the central nervous system has been studied by comparing the sizes of brain regions between species. However, more recent work has demonstrated that environmental factors, such as sensory experience, modulate brain region sizes intraspecifically, clouding the distinction between evolutionary and environmental sources of neuroanatomical variation in a sampled brain. Here, we review how teleost fish have played a central role in shaping this traditional understanding of brain structure evolution between species as well as the capacity for the environment to shape brain structure similarly within a species. By demonstrating that variation measured by brain region size varies similarly both inter- and intraspecifically, work on teleosts highlights the depth of the problem of studying brain evolution using neuroanatomy alone: even neurogenesis, the primary mechanism through which brain regions are thought to change size between species, also mediates experience-dependent changes within species. Here, we argue that teleost models also offer a solution to this overreliance on neuroanatomy in the study of brain evolution. With the advent of work on teleosts demonstrating interspecific evolutionary signatures in embryonic gene expression and the growing understanding of developmental neurogenesis as a multi-stepped process that may be differentially regulated between species, we argue that the tools are now in place to reframe how we compare brains between species. Future research can now transcend neuroanatomy to leverage the experimental utility of teleost fishes in order to gain deeper neurobiological insight to help us discern developmental signatures of evolutionary adaptation from phenotypic plasticity.

The role of neuro-epithelial-like and radial-glial stem and progenitor cells in development, plasticity, and repair.

Neural stem and progenitor cells (NSPCs) are the primary source of new neurons in the brain and serve critical roles in tissue homeostasis and plasticity throughout life. Within the vertebrate brain, NSPCs are located within distinct neurogenic niches differing in their location, cellular composition, and proliferative behaviour. Heterogeneity in the NSPC population is hypothesized to reflect varying capacities for neurogenesis, plasticity and repair between different neurogenic zones. Since the discovery of adult neurogenesis, studies have predominantly focused on the behaviour and biological significance of adult NSPCs (aNSPCs) in rodents. However, compared to rodents, who show lifelong neurogenesis in only two restricted neurogenic niches, zebrafish exhibit constitutive neurogenesis across multiple stem cell niches that provide new neurons to every major brain division. Accordingly, zebrafish are a powerful model to probe the unique cellular and molecular profiles of NSPCs and investigate how these profiles govern tissue homeostasis and regenerative plasticity within distinct stem cell populations over time. Amongst the NSPC populations residing in the zebrafish central nervous system (CNS), proliferating radial-glia, quiescent radial-glia and neuro-epithelial-like cells comprise the majority. Here, we provide insight into the extent to which these distinct NSPC populations function and mature during development, respond to experience, and contribute to successful CNS regeneration in teleost fish. Together, our review brings to light the dynamic biological roles of these individual NSPC populations and showcases their diverse regenerative modes to achieve vertebrate brain repair later in life.

Visual Experience Facilitates BDNF-Dependent Adaptive Recruitment of New Neurons in the Postembryonic Optic Tectum.

Postembryonic brain development is sensitive to environmental input and sensory experience, but the mechanisms underlying healthy adaptive brain growth are poorly understood. Here, we tested the importance of visual experience on larval zebrafish (Danio rerio) postembryonic development of the optic tectum (OT), a midbrain structure involved in visually guided behavior. We first characterized postembryonic neurogenic growth in OT, in which new neurons are generated along the caudal tectal surface and contribute appositionally to anatomical growth. Restricting visual experience during development by rearing larvae in dim light impaired OT anatomical and neurogenic growth, specifically by reducing the survival of new neurons in the medial periventricular gray zone. Neuronal survival in the OT was reduced only when visual experience was restricted for the first 5 d following new neuron generation, suggesting that tectal neurons exhibit an early sensitive period in which visual experience protects these cells from subsequent neuronal loss. The effect of dim rearing on neuronal survival was mimicked by treatment with an NMDA receptor antagonist early, but not later, in a new neuron's life. Both dim rearing and antagonist treatment reduced BDNF production in the OT, and supplementing larvae with exogenous BDNF during dim rearing prevented neuronal loss, suggesting that visual experience protects new tectal neurons through neural activity-dependent BDNF expression. Collectively, we present evidence for a sensitive period of neurogenic adaptive growth in the larval zebrafish OT that relies on visual experience-dependent mechanisms.SIGNIFICANCE STATEMENT Early brain development is shaped by environmental factors via sensory input; however, this form of experience-dependent neuroplasticity is traditionally studied as structural and functional changes within preexisting neurons. Here, we found that restricting visual experience affects development of the larval zebrafish optic tectum, a midbrain structure involved in visually guided behavior, by limiting the survival of newly generated neurons. We found that new tectal neurons exhibit a sensitive period soon after cell birth in which adequate visual experience, likely mediated by neuronal activity driving BDNF production within the tectum, would protect them from subsequent neuronal loss over the following week. Collectively, we present evidence for neurogenic adaptive tectal growth under different environmental lighting conditions.

From neurons to nests: nest-building behaviour as a model in behavioural and comparative neuroscience.

Despite centuries of observing the nest building of most extant bird species, we know surprisingly little about how birds build nests and, specifically, how the avian brain controls nest building. Here, we argue that nest building in birds may be a useful model behaviour in which to study how the brain controls behaviour. Specifically, we argue that nest building as a behavioural model provides a unique opportunity to study not only the mechanisms through which the brain controls behaviour within individuals of a single species but also how evolution may have shaped the brain to produce interspecific variation in nest-building behaviour. In this review, we outline the questions in both behavioural and comparative neuroscience that nest building could be used to address, summarize recent findings regarding the neurobiology of nest building in lab-reared zebra finches and across species building different nest structures, and suggest some future directions for the neurobiology of nest building.

Food preference and copying behaviour in zebra finches, Taeniopygia guttata.

As a social species zebra finches might be expected to copy the food choices of more experienced conspecifics. This prediction has been tested previously by presenting observers with two demonstrator birds that differ in some way (e.g., sex, familiarity), each feeding on a different colour food source. However, if the observer subsequently exhibits a preference, it is unclear whether it has copied the choice of one demonstrator or avoided the choice of the other. Furthermore, this choice may actually be influenced by pre-existing preferences, a potential bias that is rarely tested. Here we examine whether apparent copying or avoidance can be explained by pre-existing preferences. In Experiment 1, observers had the opportunity to watch a conspecific forage from one of the two differently coloured food hoppers. In Experiment 2, the observers did not have this opportunity. In both experiments observers were subsequently tested for their food hopper preference and all but one preferred one colour over the other. In Experiment 1 some observers showed evidence for copying, while others seemed to avoid the colour preferred by the demonstrator. In Experiment 2 females generally preferred the white hopper. Pre-existing colour preferences could, therefore, explain the apparent copying/avoidance we observed. This article is part of a Special Issue entitled: Cognition in the wild.

Casting a wider fish net on animal models in neuropsychiatric research.

Neuropsychiatric disorders, such as schizophrenia, are associated with abnormal brain development. In this review, we discuss how studying dimensional components of these disorders, or endophenotypes, in a wider range of animal models will deepen our understanding of how interactions between biological and environmental factors alter the trajectory of neurodevelopment leading to aberrant behavior. In particular, we discuss some of the advantages of incorporating studies of brain and behavior using a range of teleost fish species into current neuropsychiatric research. From the perspective of comparative neurobiology, teleosts share a fundamental pattern of neurodevelopment and functional brain organization with other vertebrates, including humans. These shared features provide a basis for experimentally probing the mechanisms of disease-associated brain abnormalities. Moreover, incorporating information about how behaviors have been shaped by evolution will allow us to better understand the relevance of behavioral variation to determine their physiological underpinnings. We believe that exploiting the conservation in brain development across vertebrate species, and the rich diversity of fish behavior in lab and natural populations will lead to significant new insights and a holistic understanding of the neurobiological systems implicated in neuropsychiatric disorders.

Inhibition of cell proliferation in black-capped chickadees suggests a role for neurogenesis in spatial learning.

Following development, the avian brain continues to produce neurons throughout adulthood, which functionally integrate throughout the telencephalon, including the hippocampus. In food-storing birds like the black-capped chickadee (Poecile atricapillus), new neurons incorporated into the hippocampus are hypothesized to play a role in spatial learning. Previous results on the relation between hippocampal neurogenesis and spatial learning, however, are correlational. In this study, we experimentally suppressed hippocampal neuronal recruitment and tested for subsequent effects on spatial learning in adult chickadees. After chickadees exhibited significant learning, we treated birds with daily injections of either saline or methylazoxymethanol (MAM), a toxin that suppresses cell proliferation in the brain and monitored subsequent spatial learning. MAM treatment significantly reduced cell proliferation around the lateral ventricles and neuronal recruitment in the hippocampus, measured using the cell birth marker bromodeoxyuridine. MAM-treated birds performed significantly worse than controls on the spatial learning task 12 days following the initiation of MAM treatment, a time when new neurons would begin functionally integrating into the hippocampus. This difference in learning, however, was limited to a single trial. MAM treatment did not affect any measure of body condition, suggesting learning impairments were not a product of non-specific adverse effects of MAM. This is the first evidence of a potential causal link between hippocampal neurogenesis and spatial learning in birds.

Neural correlates of nesting behavior in zebra finches (Taeniopygia guttata).

Nest building in birds involves a behavioral sequence (nest material collection and deposition in the nest) that offers a unique model for addressing how the brain sequences motor actions. In this study, we identified brain regions involved in nesting behavior in male and female zebra finches (Taeniopygia guttata). We used Fos immunohistochemistry to quantify production of the immediate early gene protein product Fos (a molecular indicator of neuronal activity) in the brain correlated this expression with the variation in nesting behavior. Using this technique, we found that neural circuitry involved in motor sequencing, social behavior, reward and motivation were active during nesting. Within pairs of nesting birds, the number of times a male picked up or deposited nesting material and the amount of time a female spent in the nest explained the variation in Fos expression in the anterior motor pathway, social behavior network, and reward neural circuits. Identification of the brain regions that are involved in nesting enables us to begin studying the roles of motor sequencing, context, and reward in construction behavior at the neural level.

Effects of corticosterone and DHEA on doublecortin immunoreactivity in the song control system and hippocampus of adult song sparrows.

Adult neuroplasticity is strongly influenced by steroids. In particular, corticosterone (CORT) and dehydroepiandrosterone (DHEA) can have opposing effects, where CORT reduces while DHEA increases neurogenesis and neuron recruitment. It has been previously shown that in adult male song sparrows, DHEA treatment increases neuron recruitment throughout the telencephalon, including the lateral ventricular zone, while the effect of CORT treatment is restricted to HVC, one of the song control regions. These data suggest that the two steroids may differentially affect proliferation, migration, differentiation, and/or survival of new neurons. To determine if CORT or DHEA alters the migration and differentiation of young neurons, we examined an endogenous marker of migrating immature neurons, doublecortin (DCX), in HVC and hippocampus of adult male song sparrows that were treated with CORT and/or DHEA for 28 days. In HVC, DHEA increased the number of DCX-labeled round cells, while CORT had no main effect on the number of DCX-labeled cells. Furthermore, DHEA increased the area covered by DCX immunoreactivity in HVC, regardless of CORT treatment. In the hippocampus, neither DHEA nor CORT affected DCX immunoreactivity. These results suggest that DHEA enhances migration and differentiation of young neurons into HVC while CORT does not affect the process, whether in the presence of DHEA or not.

Site-specific regulation of adult neurogenesis by dietary fatty acid content, vitamin E and flight exercise in European starlings.

Exercise is known to have a strong effect on neuroproliferation in mammals ranging from rodents to humans. Recent studies have also shown that fatty acids and other dietary supplements can cause an upregulation of neurogenesis. It is not known, however, how exercise and diet interact in their effects on adult neurogenesis. We examined neuronal recruitment in multiple telencephalic sites in adult male European starlings (Sturnus vulgaris) exposed to a factorial combination of flight exercise, dietary fatty acids and antioxidants. Experimental birds were flown in a wind tunnel following a training regime that mimicked the bird's natural flight behaviour. In addition to flight exercise, we manipulated the composition of dietary fatty acids and the level of enrichment with vitamin E, an antioxidant reported to enhance neuronal recruitment. We found that all three factors - flight exercise, fatty acid composition and vitamin E enrichment - regulate neuronal recruitment in a site-specific manner. We also found a robust interaction between flight training and vitamin E enrichment at multiple sites of neuronal recruitment. Specifically, flight training was found to enhance neuronal recruitment across the telencephalon, but only in birds fed a diet with a low level of vitamin E. Conversely, dietary enrichment with vitamin E upregulated neuronal recruitment, but only in birds not flown in the wind tunnel. These findings indicate conserved modulation of adult neurogenesis by exercise and diet across vertebrate taxa and indicate possible therapeutic interventions in disorders characterized by reduced adult neurogenesis.

The evolution of cerebellum structure correlates with nest complexity.

Across the brains of different bird species, the cerebellum varies greatly in the amount of surface folding (foliation). The degree of cerebellar foliation is thought to correlate positively with the processing capacity of the cerebellum, supporting complex motor abilities, particularly manipulative skills. Here, we tested this hypothesis by investigating the relationship between cerebellar foliation and species-typical nest structure in birds. Increasing complexity of nest structure is a measure of a bird's ability to manipulate nesting material into the required shape. Consistent with our hypothesis, avian cerebellar foliation increases as the complexity of the nest built increases, setting the scene for the exploration of nest building at the neural level.

Influence of testosterone metabolites on song-control system neuroplasticity during photostimulation in adult European starlings (Sturnus vulgaris).

The song-control system is a network of discrete nuclei in the songbird brain that controls the production and learning of birdsong and exhibits some of the best-studied neuroplasticity found in the adult brain. Photoperiodic growth of the song-control system during the breeding season is driven, at least in part, by the gonadal steroid testosterone. When acting on neural tissue, however, testosterone can be metabolized into 5α-dihydrotestosterone (DHT) or 17ß-estradiol (E2), which activate different hormonal signaling pathways. By treating adult starlings with both testosterone metabolites and metabolite antagonists, we attempted to isolate the effects of androgen and estrogen treatment on neuroplasticity during photostimulation in male and female European starlings (Sturnus vulgaris). Photostimulation resulted in a large HVC volume typical of the breeding season in all treatments independent of hormone treatment. E2 had additional effects on HVC growth by reducing neuron density and enhancing early survival of new neurons recruited to HVC in females but did not significantly affect HVC volume. Conversely, DHT reduced the migration of new neurons, assessed by the expression of doublecortin, to HVC. DHT also increased syrinx mass and maintained RA (robust nucleus of the arcopallium) cytoarchitecture in the presence of aromatase inhibitors. In addition, we document the first evidence of sex-specific neuroplastic responses of the song-control system to androgens and estrogens. These findings suggest that the contributions of DHT and E2 signaling in songbird neuroplasticity may be regulated by photoperiod and that future studies should account for species and sex differences in the brain.

Male bias in the song control system despite female bias in song rate in streak-backed orioles (Icterus pustulatus).

The song control system is a group of discrete interconnected nuclei found in the brains of all songbirds (suborder Passeri). Previous studies have reported a positive relationship between sex differences in song nucleus volumes and sex differences in song behavior across numerous songbird species, with species exhibiting greater sex differences in behavior also exhibiting greater sex differences in the brain. This body of comparative research, however, has failed to incorporate data from a bird species in which females sing more than males. In this study, we examine song nucleus volumes in both sexes of the streak-backed oriole (Icterus pustulatus), a New World blackbird with a female bias in song rate and similar song complexity between the sexes. Results from this neuroanatomical analysis are contrary to what was to be expected from previous research: despite the female bias in song rate, males have a significantly larger HVC and area X song nucleus volumes. Specifically, male HVC was 75% larger than that of females, and male area X was 64% larger than that of females. There was no significant sex difference in the size of the nucleus robustus arcopallialis. The lack of a positive relationship between song nuclei and singing behavior in these orioles demonstrates that our current understanding of song modulation via the song control system may be overly reliant on basic measures such as total volumes.