Dissociating ocular dominance column development and ocular dominance plasticity: a neurotrophic model

 Recent experimental data indicate that both neurotrophic factors (NTFs) and intracortical inhibitory circuitry are implicated in the development and plasticity of ocular dominance columns. We extend a neurotrophic model of developmental synaptic plasticity, which previously failed to account correctly for the differences between monocular deprivation and binocular deprivation, and show that the inclusion of lateral cortical inhibition is indeed necessary in understanding the effects of visual deprivation in the model. In particular, we argue that monocular deprivation causes a differential shift in the balance between inhibition and excitation in cortical columns, down-regulating NTFs in deprived-eye columns and up-regulating NTFs in undeprived-eye columns; during binocular deprivation, however, no such shift occurs. We thus postulate that the response to visual deprivation is at the level of the cortical circuit, while the mechanisms of afferent segregation are at the molecular or cellular level. Such a dissociation is supported by recent experimental work challenging the assumption that columnar organisation develops in an activity-dependent, competitive fashion. Our extended model also questions recent attempts to distinguish between heterosynaptic and homosynaptic models of synaptic plasticity. Received: 17 April 2001 / Accepted in revised form: 7 November 2001     

Widespread correlations between dominance and homozygous effects of mutations: implications for theories of dominance

The dominance of deleterious mutations has important consequences for phenomena such as inbreeding depression, the evolution of diploidy, and levels of natural genetic variation. Kacser and Burns' metabolic theory provides a paradigmatic explanation for why most large-effect mutations are recessive. According to the metabolic theory, the recessivity of large-effect mutations is a consequence of a diminishing-returns relationship between flux through a metabolic pathway and enzymatic activity at any step in the pathway, which in turn is an inevitable consequence of long metabolic pathways. A major line of support for this theory was the demonstration of a negative correlation between homozygous effects and dominance of mutations in Drosophila, consistent with a central prediction of the metabolic theory. Using data on gene deletions in yeast, we show that a negative correlation between homozygous effects and dominance of mutations exists for all major categories of genes analyzed, not just those encoding enzymes. The relationship between dominance and homozygous effects is similar for duplicated and single-copy genes and for genes whose products are members of protein complexes and those that are not. A complete explanation of dominance therefore requires either a generalization of Kacser and Burns' theory to nonenzyme genes or a new theory.     

Lifelong learning: ocular dominance plasticity in mouse visual cortex

Ocular dominance plasticity has long served as a successful model for examining how cortical circuits are shaped by experience. In this paradigm, altered retinal activity caused by unilateral eye-lid closure leads to dramatic shifts in the binocular response properties of neurons in the visual cortex. Much of the recent progress in identifying the cellular and molecular mechanisms underlying ocular dominance plasticity has been achieved by using the mouse as a model system. In this species, monocular deprivation initiated in adulthood also causes robust ocular dominance shifts. Research on ocular dominance plasticity in the mouse is starting to provide insight into which factors mediate and influence cortical plasticity in juvenile and adult animals.     

Development of cortical circuits: lessons from ocular dominance columns

The development of ocular dominance columns has served as a Rosetta stone for understanding the mechanisms that guide the construction of cortical circuits. Traditionally, the emergence of ocular dominance columns was thought to be closely tied to the critical period, during which columnar architecture is highly susceptible to alterations in visual input. However, recent findings in cats, monkeys and ferrets indicate that columns develop far earlier, more rapidly and with considerably greater precision than was previously suspected. These observations indicate that the initial establishment of cortical functional architecture, and its subsequent plasticity during the critical period, are distinct developmental phases that might reflect distinct mechanisms.     

Elimination of inhibitory synapses is a major component of adult ocular dominance plasticity

During development, cortical plasticity is associated with the rearrangement of excitatory connections. While these connections become more stable with age, plasticity can still be induced in the adult cortex. Here we provide evidence that structural plasticity of?inhibitory synapses onto pyramidal neurons is?a major component of plasticity in the adult neocortex. In?vivo two-photon imaging was used to monitor the formation and elimination of fluorescently labeled inhibitory structures on pyramidal neurons. We find that ocular dominance plasticity in the adult visual cortex is associated with rapid inhibitory synapse loss, especially of those present on dendritic spines. This occurs not only with monocular deprivation but also with subsequent restoration of binocular vision. We propose that in the adult visual cortex the experience-induced loss of inhibition may effectively strengthen specific visual inputs with limited need for rearranging the excitatory circuitry.     

Talent in the taxi: a model system for exploring expertise

While there is widespread interest in and admiration of individuals with exceptional talents, surprisingly little is known about the cognitive and neural mechanisms underpinning talent, and indeed how talent relates to expertise. Because many talents are first identified and nurtured in childhood, it can be difficult to determine whether talent is innate, can be acquired through extensive practice or can only be acquired in the presence of the developing brain. We sought to address some of these issues by studying healthy adults who acquired expertise in adulthood. We focused on the domain of memory and used licensed London taxi drivers as a model system. Taxi drivers have to learn the layout of 25 000 streets in London and the locations of thousands of places of interest, and pass stringent examinations in order to obtain an operating licence. Using neuropsychological assessment and structural and functional magnetic resonance imaging, we addressed a range of key questions: in the context of a fully developed brain and an average IQ, can people acquire expertise to an exceptional level; what are the neural signatures, both structural and functional, associated with the use of expertise; does expertise change the brain compared with unskilled control participants; does it confer any cognitive advantages, and similarly, does it come at a cost to other functions? By studying retired taxi drivers, we also consider what happens to their brains and behaviour when experts stop using their skill. Finally, we discuss how the expertise of taxi drivers might relate to the issue of talent and innate abilities. We suggest that exploring talent and expertise in this manner could have implications for education, rehabilitation of patients with cognitive impairments, understanding individual differences and possibly conditions such as autism where exceptional abilities can be a feature.     

The effect of dominance on food hoarding: a game theoretical model

Many food hoarding animals live in small groups structured by rank. The presence of conspecifics in the hoarding area increases the risk of losing stored supplies. The possibility of stealing from others depends on a forager's rank in the group. Highly ranked individuals can steal from subordinates and also protect their own caches. Since storing incurs both costs and benefits, the optimal hoarding investment will differ between individuals of different rank. In a game theoretical model, we investigate how dominant and subordinate individuals should optimize their hoarding effort. Our model imagines animals that are large-scale hoarders in autumn and dependent on stored supplies for winter survival. Many examples can be found in the bird families Paridae and Corvidae, but the model can be used for any hoarding species that forage in groups. Predictions from the model are as follows: First, subordinates should store more than dominants, but in a predictable environment, this difference will decrease as the environment gets harsher. Under harsh conditions, dominants should store almost as much as subordinates and, later, spend almost as much time retrieving their own caches as subordinates. Second, if on the other hand, bad winter conditions were not expected when storing, dominants should spend more time pilfering caches from subordinates. Third, in populations that are highly dependent on stored supplies, dominants should store relatively more than in populations that are less dependent on stored supplies. Fourth, harsher environments will favor hoarding. And finally, if dominant individuals store, it implies that hoarders have a selfish recovery advantage over conspecific pilferers.     

Feedback loop between kinship and dominance: the macaque model

There is growing evidence that macaque social systems represent sets of coadapted traits in which strength of hierarchies and degree of nepotism covary. A framework is developed to explain the link between dominance and kinship phenomena, assuming that power brought by alliances among non-kin is allometrically related to those involving relatives. This can account for the type of social relationships observed in "despotic" systems vs. "egalitarian" ones. When social bonds are mostly founded on kinship, lineages are closed and social power generated by coalitions among relatives may reach high levels; social power frequently outweighs the fighting abilities of single individuals, and asymmetry of dominance between group members may be marked. When lineages are more open, social bonds and alliances are less kin-biased, social relationships are more equal, and as the influence of coalitions is less important, the individual retains a certain degree of freedom in relation to the power of kin-networks. Acknowledging that the balance between individual and social power is not set at the same level across different species can explain a number of variations in rules of rank inheritance and relative dominance of males and females among macaques. The framework illustrates how epigenetic processes may shape complex features of primate social systems, and offers opportunities for testing.     

Research ethics capacity development in Africa: exploring a model for individual success

The Johns Hopkins-Fogarty African Bioethics Training Program (FABTP) has offered a fully-funded, one-year, non-degree training opportunity in research ethics to health professionals, ethics committee members, scholars, journalists and scientists from countries across sub-Saharan Africa. In the first 9 years of operation, 28 trainees from 13 African countries have trained with FABTP. Any capacity building investment requires periodic critical evaluation of the impact that training dollars produce. In this paper we describe and evaluate FABTP and the efforts of its trainees. Our data show that since 2001, the 28 former FABTP trainees have authored or co-authored 105 new bioethics-related publications; were awarded 33 bioethics-related grants; played key roles on 78 bioethics-related research studies; and participated in 198 bioethics workshops or conferences. Over the past nine years, trainees have collectively taught 48 separate courses related to bioethics and have given 170 presentations on various topics in the field. Many former trainees have pursued and completed doctoral degrees in bioethics; some have become editorial board members for bioethics journals. Female trainees were, on average, less experienced at matriculation and produced fewer post-training outputs than their male counterparts. More comprehensive studies are needed to determine the relationships between age, sex, previous experience and training program outputs.     

The ocular lens: a classic model for development, physiology and disease

Millions are rendered blind or exhibit visual impairment due to pathologies of the lens of the eye. Lens research therefore addresses the direct need to gain insights into the cellular and molecular basis of disease, but, moreover, serves as a valuable experimental system to answer fundamental biological questions. This themed issue showcases the scientific knowledge of the processes involved in the development, structure, ultrastructure, physiology and pathology of the lens and how this information has the potential to significantly further knowledge in various fields of research. The issue is divided into three main areas. Firstly, the lens is discussed as a developmental model for embryonic induction, as an elegant system for studying the role of growth factors in development, and for analysis of the molecular control and cellular basis of cellular differentiation. The genetic basis of disorders of lens development, including paediatric cataract (lens opacity), are also discussed in this section. Secondly, adult lens structure and ultrastructure are covered, as well as the lens as a model for homeostasis and solute exchange. Finally, the papers in the latter part of the special issue review lens pathology, including the lens as a model for normal and pathological ageing, vitreoretinal influences on lens function and cataract and the lens as a model for fibrotic disease. Overall, the articles highlight the lens as a continuing, very important and attractive model system for biologists working in many different research areas.     

Equilibrium correlations in a model for multidimensional epistasis

We investigate a statistical model for multidimensional epistasis. The genotype is devided into subsequences, and within each subsequence mutations which occur in a prescribed order are beneficial. The bit-string model used to represent the genotype, may be cast in the form of a ferromagnetic Ising model with a staggered field. We describe the actual correlations between mutations at different sites, within an equilibrium population at a given tolerance, which we define to be the temperature of the statistical ensemble.     

Subplate neurons regulate maturation of cortical inhibition and outcome of ocular dominance plasticity

Synaptic plasticity during critical periods of development requires intact inhibitory circuitry. We report that subplate neurons are needed both for maturation of inhibition and for the proper sign of ocular dominance (OD) plasticity. Removal of subplate neurons prevents the developmental upregulation of genes involved in mature, fast GABAergic transmission in cortical layer 4, including GABA receptor subunits and KCC2, and thus prevents the switch to a hyperpolarizing effect of GABA. To understand the implications of these changes, a realistic circuit model was formulated. Simulations predicted that without subplate neurons, monocular deprivation (MD) paradoxically favors LGN axons representing the deprived (less active) eye, exactly what was then observed experimentally. Simulations also account for published results showing that OD plasticity requires mature inhibition. Thus, subplate neurons regulate molecular machinery required to establish an adult balance of excitation and inhibition in layer 4, and thereby influence the outcome of OD plasticity.     

HMMSTR: a hidden Markov model for local sequence-structure correlations in proteins

We describe a hidden Markov model, HMMSTR, for general protein sequence based on the I-sites library of sequence-structure motifs. Unlike the linear hidden Markov models used to model individual protein families, HMMSTR has a highly branched topology and captures recurrent local features of protein sequences and structures that transcend protein family boundaries. The model extends the I-sites library by describing the adjacencies of different sequence-structure motifs as observed in the protein database and, by representing overlapping motifs in a much more compact form, achieves a great reduction in parameters. The HMM attributes a considerably higher probability to coding sequence than does an equivalent dipeptide model, predicts secondary structure with an accuracy of 74.3 %, backbone torsion angles better than any previously reported method and the structural context of beta strands and turns with an accuracy that should be useful for tertiary structure prediction.     

Polistes paper wasps: a model genus for the study of social dominance hierarchies

Polistes are an ideal system to study ultimate and proximate questions of dominance, and to test theoretical predictions about social evolution. The behaviors typically associated with dominance in Polistes are similar to those observed in many vertebrate societies. Here, we review recent ethological, mechanistic, and evolutionary studies on how social dominance hierarchies are established and maintained in Polistes spp. From the ultimate perspective, we address individual and group benefits of hierarchy formation, as well as issues such as reproductive skew, queen-worker conflict, and costs of challenging the dominant. From the proximate perspective, we review social, physical, and physiological factors influencing hierarchy formation, including co-foundress interactions, age structure, body size, endocrine system, and chemical and visual signals. We also discuss the extensive inter- and intra-specific variation of Polistes in the formation and maintenance of hierarchies, as well as levels of within-colony aggression. We conclude the review by highlighting the utility of this variation for comparative studies and the immense potential of the genus Polistes to address fundamental and unanswered questions about the evolution and maintenance of dominance behavior in animals.