A blueprint for vocal learning: auditory predispositions from brains to genomes

Memorizing and producing complex strings of sound are requirements for spoken human language. We share these behaviours with likely more than 4000 species of songbirds, making birds our primary model for studying the cognitive basis of vocal learning and, more generally, an important model for how memories are encoded in the brain. In songbirds, as in humans, the sounds that a juvenile learns later in life depend on auditory memories formed early in development. Experiments on a wide variety of songbird species suggest that the formation and lability of these auditory memories, in turn, depend on auditory predispositions that stimulate learning when a juvenile hears relevant, species-typical sounds. We review evidence that variation in key features of these auditory predispositions are determined by variation in genes underlying the development of the auditory system. We argue that increased investigation of the neuronal basis of auditory predispositions expressed early in life in combination with modern comparative genomic approaches may provide insights into the evolution of vocal learning.     

Bridging behavior and other affiliative interactions among male tibetan macaques (Macaca thibetana)

I describe bridging behavior and social relationships between adult males and infants in a free- ranging group of Tibetan macaques (Macaca thibetana)at Mt. Huangshan, China. The subjects performed bridging in which two adult males simultaneously lifted up an infant, sucked or touched its genitalia, and then groomed each other in nonagonistic contexts. Males also expressed social behaviors with other males, such as mounting, penis-sucking, and embracing while touching each other’s penes. Males also employ bridging while exploiting an infant as a social tool, not only to reduce the probability of an aggressive response from dominant males (agonistic buffering), but also to develop and to maintain affiliative social relationships with other males. Use of male infants in bridging contributed to frequent male-infant interactions such as holding,grooming, and penis-sucking. Although these interactions might not have a positive influence on infant survival, they may facilitate the maintenance of affiliative relationships with adult males until they reach maturity. The development of bridging might have a close relation to the high socionomic sex ratio (adult male/adult female) and frequent affiliative interactions between males, especially among the adolescents and adults.     

Paradox of peramorphic paedomorphosis: Heterochrony and human evolution

This paper reviews Gould's clock model for heterochronic processes and uses that model to develop simple matrix representations of growth and shape change. Matrix representations of growth and development provide a common formulation for all heterochronic processes. In particular, we show how neoteny can be diagnosed using such a matrix approach. The literature is rife with contradictory representations of how neoteny affects growth allometries and the timing of developmental events, and therefore of the role of neoteny in human evolution. Through the use of multivariate models, we explore these relationships and the internal consistency of opposing views. Gould's neoteny hypothesis for human evolution has been criticized for a number of reasons. Humans do not grow slowly. The slopes of our growth allometries show no common pattern of change vis-a-vis those of our closest relatives. Humans prolong rather than reduce rates of growth and development of body parts; the brain, for example, ceases growing later in humans than in apes, but during this prolonged period of early ontogeny, it grows at a rapid pace. This paper evaluates Gould's hypothesis and its critiques by focusing on particular questions. Does neoteny imply slow growth? Does it imply a unidirectional change in the rates of growth of traits? Under neoteny, should the brain cease growing in ancestor and descendant at the same age? Does prolongation of phases of growth and development confute neoteny? On the other hand, is paedomorphosis an inevitable consequence of prolonged growth and development? We show that, for all of these questions, the answer is no. © 1996 Wiley-Liss, Inc.     

Postnatal Development of Cholinergic Enzymes and Receptors in Mouse Brain

The developmental profiles for the cholinergic enzymes acetylcholinesterase and choline acetyltransferase, and the muscarinic and nicotinic receptors were determined in whole mouse brain. The enzyme activities (per milligram of protein) increased steadily from birth, reaching adult levels at 20 days of age. These increases were primarily due to increases in Vmax. Muscarinic receptor numbers, measured by [3H]quinuclidinyl benzilate binding, also increased from birth to 25 days of age. Brain nicotinic receptors were measured with the ligands L-[3H]nicotine and alpha-[125I]-bungarotoxin. Neonatal mouse brain had approximately twice the number of alpha-bungarotoxin binding sites found in adult mouse brain. Binding site numbers rose slightly until 10 days of age, after which they decreased to adult values, which were reached at 25 days of age. The nicotine binding site was found in neonatal brain at concentrations comparable to those at the alpha-bungarotoxin site followed by a steady decline in nicotine binding until adult values were reached. Thus, brain nicotinic and muscarinic systems develop in totally different fashions; the quantity of muscarinic receptors increases with age, while the quantity of nicotinic receptors decreases. It is conceivable that nicotinic receptors play an important role in directing the development of the cholinergic system.     

Steroid-induced hippocampal synaptic plasticity: sex differences and similarities

Early in development, steroid hormones structurally organize various regions of the CNS. However, steroid hormones continue to affect the structure and function of the CNS throughout the life of the individual. In this review, we discuss sex differences and similarities in steroid-induced synaptic plasticity in the adult brain. Particular emphasis is placed on steroid-induced plasticity in the hippocampus, a brain region important in learning and memory. This topic is relevant to the growing evidence for the actions of sex hormones outside of the reproductive neuroendocrine axis. It also tells an important and emerging story about non-genomic and genomic actions of steroids at the cellular and molecular levels. Specifically, the effects of estrogen and progesterone as well as the androgens and glucocorticoids are discussed. The influence of steroids on hippocampal structure and function can differ vastly between the sexes. However, there are certain similarities that might aid in our understanding of how steroids affect CNS plasticity in general. Although future studies will undoubtedly lead us to a greater understanding of these phenomena, the data reviewed indicate that when studying synaptic plasticity, the sex and hormonal milieu of the individual might significantly influence the outcome and interpretation of the research.     

Mandatory " enriched" housing of laboratory animals: the need for evidence-based evaluation

Environmental enrichment for laboratory animals has come to be viewed as a potential method for improving animal well-being in addition to its original sense as a paradigm for learning how experience molds the brain. It is suggested that the term housing supplementation better describes the wide range of alterations to laboratory animal housing that has been proposed or investigated. Changes in the environments of animals have important effects on brain structure, physiology, and behavior--including recovery from illness and injury--and on which genes are expressed in various organs. Studies are reviewed that show how the brain and other organs respond to environmental change. These data warrant caution that minor cage supplementation intended for improvement of animal well-being may alter important aspects of an animal's physiology and development in a manner not easily predicted from available research. Thus, various forms of housing supplementation, although utilized or even preferred by the animals, may not enhance laboratory animal well-being and may be detrimental to the research for which the laboratory animals are used.     

Pandora's growing box: Inferring the evolution and development of hominin brains from endocasts

The brain of modern humans is an evolutionary and developmental outlier: At birth, it has the size of an adult chimpanzee brain and expands by a factor of 2 during the first postnatal year. Large neonatal brain size and rapid initial growth contrast with slow maturation, which extends well into adolescence. When, how, and why this peculiar pattern of brain ontogeny evolved and how it is correlated with structural changes in the brain are key questions of paleoanthropology. Because brains and their ontogenies do not fossilize, indirect evidence from fossil hominin endocasts needs to be combined with evidence from modern humans and our closest living relatives, the great apes. New fossil finds permit a denser sampling of hominin endocranial morphologies along ontogenetic and evolutionary time lines. New brain imaging methods provide the basis for quantifying endocast‐brain relationships and tracking endocranial and brain growth and development noninvasively. Combining this evidence with ever‐more detailed knowledge about actual and fossil “brain genes,” we are now beginning to understand how brain ontogeny and structure were modified during human evolution and what the adaptive significance of these modifications may have been.     

Changes in neuronal DNA content variation in the human brain during aging

The human brain has been proposed to represent a genetic mosaic, containing a small but constant number of neurons with an amount of DNA exceeding the diploid level that appear to be generated through various chromosome segregation defects initially. While a portion of these cells apparently die during development, neurons with abnormal chromosomal copy number have been identified in the mature brain. This genomic alteration might to lead to chromosomal instability affecting neuronal viability and could thus contribute to age-related mental disorders. Changes in the frequency of neurons with such structural genomic variation in the adult and aging brain, however, are unknown. Here, we quantified the frequency of neurons with a more than diploid DNA content in the cerebral cortex of normal human brain and analyzed its changes between the fourth and ninth decades of life. We applied a protocol of slide-based cytometry optimized for DNA quantification of single identified neurons, which allowed to analyze the DNA content of about 500 000 neurons for each brain. On average, 11.5% of cortical neurons showed DNA content above the diploid level. The frequency of neurons with this genomic alteration was highest at younger age and declined with age. Our results indicate that the genomic variation associated with DNA content exceeding the diploid level might compromise viability of these neurons in the aging brain and might thus contribute to susceptibilities for age-related CNS disorders. Alternatively, a potential selection bias of "healthy aging brains" needs to be considered, assuming that DNA content variation above a certain threshold associates with Alzheimer's disease.     

The natural regulation of buffalo populations in East Africa: III. Population trends and mortality*

Analysis is carried out on the population data obtained from censuses and estimates of fertility and recruitment for the years 1965–1972, From the analysis, adult mortality is the only detectable reduction which acts as a negative feedback on the population, and is the only one needed to regulate the population in a way similar to the observed population trends. From a frequency distribution of ages at death, an approximate composite life table is constructed. This shows that males and females have similar age-specific mortalities until old age, but then males survive relatively better. Information on the causes of mortality indicate that the regulating adult mortality is caused in part by undernutrition, which in turn is due to food limitation rather than to social and physiological factors. Predation causes only a small part of the annual adult mortality, and its effect is swamped by other factors. Diseases play an important part as a primary factor in juvenile mortality but not in adult mortality because of the development of immunity. However, both disease and predation are important as secondary agents killing adults already weakened by moderate undernutrition. It is suggested that they play an essential role by hastening the population's response to changes in the food supply, and hence dampening oscillations that might develop in population and resource.     

Mad2 and spindle assembly checkpoint function during meiosis I in mammalian oocytes

During mammalian mitosis, a proofreading network called the spindle assembly checkpoint (SAC) is indispensable for ensuring the fidelity of chromosome segregation. An inhibitory SAC signal is deputed to inhibits mitotic cell-cycle progression in response to misaligned chromosomes until such imperfections are rectified thereby ensuring equitable chromosome partitioning to daughter cells. Amongst the cast of SAC proteins, mitotic arrest deficient 2 (Mad2) plays a leading role in transducing the SAC signal. The aneuploidy and cancer predispositions of individuals who harbour genetic mutations in SAC genes emphasise the in vivo significance of this surveillance mechanism. In humans, congenital aneuploidies such as Down's syndrome demonstrate an exponential increase with advancing female age. Although largely the result of female meiosis I errors, the molecular entities that succumb with age in oocytes remain elusive. Declining oocyte SAC function could plausibly contribute to such errors. Until recently however, convincing evidence for a functional SAC in mammalian oocytes during meiosis I was unforthcoming. Here I review the evidence regarding the SAC in female mammalian meiosis I and how our understanding of this system has evolved in recent years. This review will focus on Mad2 as this is the SAC protein that has been most comprehensively investigated.     

Allosteric activation of brain hexokinase by magnesium ions and by magnesium-ion–adenosine triphosphate complex

1. The highest blood concentrations of ketone bodies were found at 5 days of age, after which time the concentration fell to reach the adult value by 30 days of age. 2. Both mitochondrial and cytoplasmic hydroxymethylglutaryl-CoA synthase activities were detected, with highest activities being found in the mitochondria at all stages of development. Activity of the mitochondrial enzyme increases rapidly immediately after birth, showing a maximum at 15 days of age, thereafter falling to adult values. The cytoplasmic enzyme, on the other hand, increased steadily in activity after birth to reach a maximum at 40 days of age, after which time activity fell to adult values. 3. Both mitochondrial and cytoplasmic aceto-acetyl-CoA thiolase activities were detected, with the mitochondrial enzyme having considerably higher activities at all stages of development. The developmental patterns for both enzymes were very similar to those for the corresponding hydroxymethylglutaryl-CoA synthases. 4. The activity of heart acetoacetyl-CoA transferase remains constant from late foetal life until the end of the suckling period, after which time there is a gradual threefold increase in activity to reach the adult values. The activity of brain 3-oxo acid CoA-transferase increases steadily after birth, reaching a maximum at 30 days of age, thereafter decreasing to adult values, which are similar to foetal activities. Although at all stages of development the specific activity of the heart enzyme is higher than that of brain, the total enzymic capacity of the brain is higher than that of the heart during the suckling period.     

The Predictive Value of Early Behavioural Assessments in Pet Dogs – A Longitudinal Study from Neonates to Adults

Studies on behavioural development in domestic dogs are of relevance for matching puppies with the right families, identifying predispositions for behavioural problems at an early stage, and predicting suitability for service dog work, police or military service. The literature is, however, inconsistent regarding the predictive value of tests performed during the socialisation period. Additionally, some practitioners use tests with neonates to complement later assessments for selecting puppies as working dogs, but these have not been validated. We here present longitudinal data on a cohort of Border collies, followed up from neonate age until adulthood. A neonate test was conducted with 99 Border collie puppies aged 2–10 days to assess activity, vocalisations when isolated and sucking force. At the age of 40–50 days, 134 puppies (including 93 tested as neonates) were tested in a puppy test at their breeders'' homes. All dogs were adopted as pet dogs and 50 of them participated in a behavioural test at the age of 1.5 to 2 years with their owners. Linear mixed models found little correspondence between individuals'' behaviour in the neonate, puppy and adult test. Exploratory activity was the only behaviour that was significantly correlated between the puppy and the adult test. We conclude that the predictive validity of early tests for predicting specific behavioural traits in adult pet dogs is limited.     

Immunohistochemical localization of the early embryonic antigen (SSEA-1) in postimplantation mouse embryos and fetal and adult tissues

Distribution of the stage-specific embryonic antigen (SSEA-1) was studied in postimplantation murine embryos, fetuses, and adult mice by immunohistochemical techniques. SSEA-1 was also localized on the stem cells of differentiating solid teratocarcinomas and on the surface of core cells of solid embryoid bodies. At the egg cylinder stage the antigen is restricted to embryonic ectoderm and visceral endoderm. During subsequent development SSEA-1 becomes localized to portions of the brain and primordial germ cells. In addition some sites of the urogenital anlage are SSEA-1 positive. In adult mice, the epithelium of the oviduct, the endometrium, and the epididymis are the cells most reactive with the monoclonal antibody to SSEA-1; although some areas of the brain and kidney tubules are weakly positive. Study of this antigenic determinant might disclose some previously unexpected cell lineage relationships and/or might elucidate events necessary for reproduction.     

NAD+ controls neural stem cell fate in the aging brain

Loss of the coenzyme NAD⁺, which is required for many energy‐dependent cellular processes, has emerged as a potentially unifying mechanism for age‐related conditions. A study in this issue of The EMBO Journal identifies a novel link between depletion of NAD⁺ and age‐associated loss of proliferating adult neural stem/progenitor cells in the murine brain (Stein & Imai, 2014 ). These data have important implications for how brain function might decline with age.     

MNB/DYRK1A as a multiple regulator of neuronal development

MNB/DYRK1A is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family that has been strongly conserved across evolution. There are substantial data implicating MNB/DYRK1A in brain development and adult brain function, as well as in neurodegeneration and Down syndrome pathologies. Here we review our current understanding of the neurodevelopmental activity of MNB/DYRK1A. We discuss how MNB/DYRK1A fulfils several sequential roles in neuronal development and the molecular mechanisms possibly underlying these functions. We also summarize the evidence behind the hypotheses to explain how the imbalance in MNB/DYRK1A gene dosage might be implicated in the neurodevelopmental alterations associated with Down syndrome. Finally, we highlight some research directions that may help to clarify the mechanisms and functions of MNB/DYRK1A signalling in the developing brain.     

Ion channel regulation by β-secretase BACE1 – enzymatic and non-enzymatic effects beyond Alzheimer's disease

β-site APP-cleaving enzyme 1 (BACE1) has become infamous for its pivotal role in the pathogenesis of Alzheimer's disease (AD). Consequently, BACE1 represents a prime target in drug development. Despite its detrimental involvement in AD, it should be quite obvious that BACE1 is not primarily present in the brain to drive mental decline. In fact, additional functions have been identified. In this review, we focus on the regulation of ion channels, specifically voltage-gated sodium and KCNQ potassium channels, by BACE1. These studies provide evidence for a highly unexpected feature in the functional repertoire of BACE1. Although capable of cleaving accessory channel subunits, BACE1 exerts many of its physiologically significant effects through direct, non-enzymatic interactions with main channel subunits. We discuss how the underlying mechanisms can be conceived and develop scenarios how the regulation of ion conductances by BACE1 might shape electric activity in the intact and diseased brain and heart.     

The neuroeconomic path of the law

Advances in evolutionary biology, experimental economics and neuroscience are shedding new light on age-old questions about right and wrong, justice, freedom, the rule of law and the relationship between the individual and the state. Evidence is beginning to accumulate suggesting that humans evolved certain fundamental behavioural predispositions grounded in our intense social natures, that those predispositions are encoded in our brains as a distribution of probable behaviours, and therefore that there may be a core of universal human law.     

Larval habitats impose trait-dependent limits on the direction and rate of adult evolution in dragonflies

Natural selection on juveniles is often invoked as a constraint on adult evolution, but it remains unclear when such restrictions will have their greatest impact. Selection on juveniles could, for example, mainly limit the evolution of adult traits that mostly develop prior to maturity. Alternatively, selection on juveniles might primarily constrain the evolution of adult traits that experience weak or context-dependent selection in the adult stage. Using a comparative study of dragonflies, I tested these hypotheses by examining how a species’ larval habitat was related to the evolution of two adult traits that differ in development and exposure to selection: adult size and male ornamentation. Whereas adult size is fixed at metamorphosis and experiences consistent positive selection in the adult stage, ornaments develop throughout adulthood and provide context-dependent fitness benefits. My results show that species that develop in less stable larval habitats have smaller adult sizes and slower rates of adult size evolution. However, these risky larval habitats do not limit ornament expression or rates of ornament evolution. Selection on juveniles may therefore primarily affect the evolution of adult traits that mostly develop prior to maturity.     

Stem cells in brain tumorigenesis and their impact on therapy

The concept that the genesis of new cells in the adult mammalian brain is negligible has long influenced our perception and understanding of the origin and development of central nervous system (CNS) tumors. The discovery that neurons and glia are produced throughout life from neural stem cells provides new possibilities for candidate precursor cells of CNS neoplasms. The emerging hypothesis is that alterations in the cellular and genetic mechanisms that control adult neurogenesis might contribute to brain tumorigenesis. As such, opportunities become available to identify new therapeutic strategies.