Building a bird brain: Sculpting neural circuits for a learned behavior

Development in animals is frequently characterized by periods of heightened capacity for both neural and behavioral change. So-called sensitive periods of development are windows of opportunity in which brain and behavior are most susceptible to modification. Understanding what factors regulate sensitive periods constitutes one of the main goals of developmental neuroscience. Why is the ability to learn complex behavioral patterns often restricted to sensitive periods of development? Songbirds provide a model system for unraveling the mysteries of neural mechanisms of learning during development. Like many songbirds, zebra finches (Taeniopygia guttata) learn a specific vocal pattern during a restricted period early in life. Young birds must hear songs produced by members of their species; this auditory experience is thought to engender specific changes in the brain to guide the process of vocal learning. Many studies of the songbird system have focused on examining relationships between brain development and learning. One goal of this work is to elucidate mechanisms that regulate basic processes of neural development, and in so doing to shed light on factors governing the emergence of a complex learned behavior.     

Moral intuition: Its neural substrates and normative significance

Philosophers use the phrase "moral intuition" to describe the appearance in consciousness of moral judgments or assessments without any awareness of having gone through a conscious reasoning process that produces this assessment. This paper investigates the neural substrates of moral intuition. We propose that moral intuitions are part of a larger set of social intuitions that guide us through complex, highly uncertain and rapidly changing social interactions. Such intuitions are shaped by learning. The neural substrates for moral intuition include fronto-insular, cingulate, and orbito-frontal cortices and associated subcortical structure such as the septum, basil ganglia and amygdala. Understanding the role of these structures undercuts many philosophical doctrines concerning the status of moral intuitions, but vindicates the claim that they can sometimes play a legitimate role in moral decision-making.     

Well-being and affective style: neural substrates and biobehavioural correlates

One of the most salient features of emotion is the pronounced variability among individuals in their reactions to emotional incentives and in their dispositional mood. Collectively, these individual differences have been described as affective style. Recent research has begun to dissect the constituents of affective style. The search for these components is guided by the neural systems that instantiate emotion and emotion regulation. In this article, this body of research and theory is applied specifically to positive affect and well-being. The central substrates and peripheral biological correlates of well-being are described. A resilient affective style is associated with high levels of left prefrontal activation, effective modulation of activation in the amygdala and fast recovery in response to negative and stressful events. In peripheral biology, these central patterns are associated with lower levels of basal cortisol and with higher levels of antibody titres to influenza vaccine. The article concludes with a consideration of whether these patterns of central and peripheral biology can be modified by training and shifted toward a more salubrious direction.     

Functional dissection of the neural substrates for sexual behaviors in Drosophila melanogaster

The male-specific Fruitless proteins (FruM) act to establish the potential for male courtship behavior in Drosophila melanogaster and are expressed in small groups of neurons throughout the nervous system. We screened ～1000 GAL4 lines, using assays for general courtship, male-male interactions, and male fertility to determine the phenotypes resulting from the GAL4-driven inhibition of FruM expression in subsets of these neurons. A battery of secondary assays showed that the phenotypic classes of GAL4 lines could be divided into subgroups on the basis of additional neurobiological and behavioral criteria. For example, in some lines, restoration of FruM expression in cholinergic neurons restores fertility or reduces male-male courtship. Persistent chains of males courting each other in some lines results from males courting both sexes indiscriminately, whereas in other lines this phenotype results from apparent habituation deficits. Inhibition of ectopic FruM expression in females, in populations of neurons where FruM is necessary for male fertility, can rescue female infertility. To identify the neurons responsible for some of the observed behavioral alterations, we determined the overlap between the identified GAL4 lines and endogenous FruM expression in lines with fertility defects. The GAL4 lines causing fertility defects generally had widespread overlap with FruM expression in many regions of the nervous system, suggesting likely redundant FruM-expressing neuronal pathways capable of conferring male fertility. From associations between the screened behaviors, we propose a functional model for courtship initiation.     

Ecological hazard/risk assessment: lessons learned and new directions

A series of workshops held in the 1970s and 1980s, beginning at the University of Michigan Biological Station near Pellston, Michigan (and thus called the Pellston Series), focused on identifying the basic tenets of ecological hazard/risk assessment. The purpose of this discussion, produced roughly two decades after the first Pellston workshop, is to examine the impacts of this series on the development of the ecological hazard/risk assessment process, to explore some barriers hindering the development of this process, and suggest some new directions and challenges yet unaddressed by any of the workshop series. Probably the most important factor identified since the series of workshops began is persuasive circumstantial evidence that the learning process proceeds at different rates for individuals and institutions both in the government and private sectors, including academe. Evidence presently available suggests that individuals are frequently two or three decades ahead of institutions, and some individuals have already rejected paradigms generally accepted by the profession and are developing new ones. The major contribution of the workshops to the profession was connecting toxicity with environmental fate and transformation of chemicals and thus, bioavailability. Astonishingly, before the first Pellston workshop, this now-obvious connection did not play a dominant role in the peer-reviewed professional literature or in government documents, although the indefatigable investigator could find some minor indications that some professionals were aware of the importance of these relationships. Major suggestions for new directions and challenges focus on: (1) an emphasis on ecosystem health or condition rather than on mere absence of deleterious effects; (2) entering the information age requires that the type of information discussed here be integrated with and related to the broader array of other types of information used in making decisions at the societal or system level — failure to do so will mean that hazard/risk information will have little or no impact; (3) restoration ecology must emerge as a field of considerable importance because inevitably some estimates of hazard/risk will be inaccurate and damage will be done to ecosystems, which must then be repaired; (4) for all of this to function, environmental literacy must be markedly improved over its present level.     

A mathematical model for selective differentiation of neural progenitor cells on micropatterned polymer substrates

The biological hypothesis that the astrocyte-secreted cytokine, interleukin-6 (IL6), stimulates differentiation of adult rat hippocampal progenitor cells (AHPCs) is considered from a mathematical perspective. The proposed mathematical model includes two different mechanisms for stimulation and is based on mass-action kinetics. Both biological mechanisms involve sequential binding, with one pathway solely utilizing surface receptors while the other pathway also involves soluble receptors. Choosing biologically-reasonable values for parameters, simulations of the mathematical model show good agreement with experimental results. A global sensitivity analysis is also conducted to determine both the most influential and non-influential parameters on cellular differentiation, providing additional insights into the biological mechanisms.     

Juvenile hormone drives the maturation of spontaneous mushroom body neural activity and learned behavior

1. Download : Download high-res image (155KB)
2. Download : Download full-size image

     

A learned neural network that simulates properties of the neuronal population vector

This paper considers steady-state and timedependent characteristics of the response of the hidden-layer neurons in a dynamic model for the neural network trained through supervised learning to perform transformation of input signals into output signals. This transformation is set up so as to correspond to variation in the directions of two-dimensional vectors and is treated as creation by the network of a movement direction in response to a stimulus direction. The input vector is encoded in the state of the input layer at the initial instant of time, and the output vector in the state of the output layer at great values of time. After the network has been trained on examples of the input-output relation, the hidden neurons turn out to be broadly tuned to direction. The corresponding dependence for their activity is approximated with a smooth function, whose maximum allows some preferred direction to be attributed to each neuron. If each hidden neuron is assigned a vector pointing in its preferred direction, then any arbitrarily chosen direction can be characterized by an imaginary neuronal population vector (Georgopoulos et al. 1986) defined as the sum of the vectors of preferred direction for the neurons, with the weights equal to their activities for the chosen direction. It is demonstrated that, although hidden neurons are broadly tuned to direction, the population vector points in a direction congruent with that of the input vector at the initial moment of time and accurately predicts the direction of the output vector at great values of time. In between, the population vector turns continuously from the one direction towards the other. The dynamic and stationary properties of the population vector of the hidden-layer neurons, as obtained within the framework of the model in question, show a close similarity to the experimentally observed (Georgopoulos et al. 1986; Georgopoulos et al. 1989) behaviour of the population vector constructed in the same manner on the ensemble of motor cortex neurons sensitive to a certain type of movement.     

Control of neural stem cell survival by electroactive polymer substrates

Stem cell function is regulated by intrinsic as well as microenvironmental factors, including chemical and mechanical signals. Conducting polymer-based cell culture substrates provide a powerful tool to control both chemical and physical stimuli sensed by stem cells. Here we show that polypyrrole (PPy), a commonly used conducting polymer, can be tailored to modulate survival and maintenance of rat fetal neural stem cells (NSCs). NSCs cultured on PPy substrates containing different counter ions, dodecylbenzenesulfonate (DBS), tosylate (TsO), perchlorate (ClO(4)) and chloride (Cl), showed a distinct correlation between PPy counter ion and cell viability. Specifically, NSC viability was high on PPy(DBS) but low on PPy containing TsO, ClO(4) and Cl. On PPy(DBS), NSC proliferation and differentiation was comparable to standard NSC culture on tissue culture polystyrene. Electrical reduction of PPy(DBS) created a switch for neural stem cell viability, with widespread cell death upon polymer reduction. Coating the PPy(DBS) films with a gel layer composed of a basement membrane matrix efficiently prevented loss of cell viability upon polymer reduction. Here we have defined conditions for the biocompatibility of PPy substrates with NSC culture, critical for the development of devices based on conducting polymers interfacing with NSCs.     

Early induction of neural crest cells: lessons learned from frog,fish and chick

The identification of genes in Xenopus, chick and zebrafish expressed early in prospective neural crest (NC) cells has challenged the previous view that the NC is induced during the closure of the neural tube. We compare here the early inductive molecular mechanisms in different organisms and, despite observed differences, propose a general common model for NC induction.     

Culture-sensitive neural substrates of human cognition: a transcultural neuroimaging approach

Our brains and minds are shaped by our experiences, which mainly occur in the context of the culture in which we develop and live. Although psychologists have provided abundant evidence for diversity of human cognition and behaviour across cultures, the question of whether the neural correlates of human cognition are also culture-dependent is often not considered by neuroscientists. However, recent transcultural neuroimaging studies have demonstrated that one's cultural background can influence the neural activity that underlies both high- and low-level cognitive functions. The findings provide a novel approach by which to distinguish culture-sensitive from culture-invariant neural mechanisms of human cognition.     

The neural basis of financial risk taking

Investors systematically deviate from rationality when making financial decisions, yet the mechanisms responsible for these deviations have not been identified. Using event-related fMRI, we examined whether anticipatory neural activity would predict optimal and suboptimal choices in a financial decision-making task. We characterized two types of deviations from the optimal investment strategy of a rational risk-neutral agent as risk-seeking mistakes and risk-aversion mistakes. Nucleus accumbens activation preceded risky choices as well as risk-seeking mistakes, while anterior insula activation preceded riskless choices as well as risk-aversion mistakes. These findings suggest that distinct neural circuits linked to anticipatory affect promote different types of financial choices and indicate that excessive activation of these circuits may lead to investing mistakes. Thus, consideration of anticipatory neural mechanisms may add predictive power to the rational actor model of economic decision making.     

Sensitive periods and circuits for learned birdsong

Experience influences the development of certain behaviors and their associated neural circuits during a discrete period after birth. Songbirds, with their highly quantifiable vocal output and well-delineated vocal control circuitry, provide an excellent context in which to examine the neural mechanisms regulating sensitive periods for learning. Recent discoveries indicate that auditory input to the vocal control circuitry in songbirds is dynamically modulated and show that neural circuitry previously thought to be used only in plastic juvenile song may also actively maintain stable adult song. These findings provide important clues to how sensitive periods for auditory feedback and vocal plasticity are regulated during song development.     

Neural correlates of threat perception: neural equivalence of conspecific and heterospecific mobbing calls is learned

Songbird auditory areas (i.e., CMM and NCM) are preferentially activated to playback of conspecific vocalizations relative to heterospecific and arbitrary noise. Here, we asked if the neural response to auditory stimulation is not simply preferential for conspecific vocalizations but also for the information conveyed by the vocalization. Black-capped chickadees use their chick-a-dee mobbing call to recruit conspecifics and other avian species to mob perched predators. Mobbing calls produced in response to smaller, higher-threat predators contain more "D" notes compared to those produced in response to larger, lower-threat predators and thus convey the degree of threat of predators. We specifically asked whether the neural response varies with the degree of threat conveyed by the mobbing calls of chickadees and whether the neural response is the same for actual predator calls that correspond to the degree of threat of the chickadee mobbing calls. Our results demonstrate that, as degree of threat increases in conspecific chickadee mobbing calls, there is a corresponding increase in immediate early gene (IEG) expression in telencephalic auditory areas. We also demonstrate that as the degree of threat increases for the heterospecific predator, there is a corresponding increase in IEG expression in the auditory areas. Furthermore, there was no significant difference in the amount IEG expression between conspecific mobbing calls or heterospecific predator calls that were the same degree of threat. In a second experiment, using hand-reared chickadees without predator experience, we found more IEG expression in response to mobbing calls than corresponding predator calls, indicating that degree of threat is learned. Our results demonstrate that degree of threat corresponds to neural activity in the auditory areas and that threat can be conveyed by different species signals and that these signals must be learned.     

Comparative diagnostic value of methods for detecting dysentery antigens in substrates of the patient's body

The comparative evaluation of different immunological methods, such as the enzyme immunoassay, the aggregate hemagglutination test and the complement fixation test, used for the detection of specific Shigella antigens in biological body substrates obtained from 287 patients with acute dysentery caused by S. sonnei, S. flexneri and S. newcastle has been carried out. The enzyme immunoassay and the aggregate hemagglutination test most effective (97.5 +/- 0.5 and 92.4 +/- 0.9, respectively), the object of study being the patients' blood taken at the early stages of the disease. The diagnostic specificity of these methods has proved to be 98.7 +/- 6.7 and 95.2 +/- 1.4, respectively.     

Human spatial navigation: cognitive maps, sexual dimorphism, and neural substrates.

Recent research on navigation has been particularly notable for the increased understanding of the factors affecting human navigation and the neural networks supporting it. The use of virtual reality environments has made it possible to explore the effect of environment layout and content on way-finding performance, and it has shown that these effects may interact with the sex and age of subjects. Functional brain imaging, combined with the use of virtual environments, has revealed strong parallels between humans and other animals in the neural basis of navigation.