Complex Vertebrate Research Articles

Multiplexed Population Coding of Stimulus Properties by Leech Mechanosensory Cells.

Multiplexing, the simultaneous encoding of different stimulus properties by distinct neuronal response features, has recently been suggested as a mechanism used in several sensory systems, including primate somatosensation. While a rigorous experimental verification of the multiplexing hypothesis is difficult to accomplish in a complex vertebrate system, it is feasible for a small population of individually characterized leech neurons. Monitoring the responses of all four mechanoreceptors innervating a patch of skin revealed striking similarities between touch encoding in the primate and the leech: summed spike counts represent stimulus intensity, whereas relative timing of first spikes encodes stimulus location. These findings suggest that multiplexed population coding is a general mechanism of touch encoding common to species as different as man and worm.

Commentary: Blurring Borders: Innate Immunity with Adaptive Features.

Commentary: Blurring Borders: Innate Immunity with Adaptive Features.

Histology and affinity of anaspids, and the early evolution of the vertebrate dermal skeleton.

The assembly of the gnathostome bodyplan constitutes a formative episode in vertebrate evolutionary history, an interval in which the mineralized skeleton and its canonical suite of cell and tissue types originated. Fossil jawless fishes, assigned to the gnathostome stem-lineage, provide an unparalleled insight into the origin and evolution of the skeleton, hindered only by uncertainty over the phylogenetic position and evolutionary significance of key clades. Chief among these are the jawless anaspids, whose skeletal composition, a rich source of phylogenetic information, is poorly characterized. Here we survey the histology of representatives spanning anaspid diversity and infer their generalized skeletal architecture. The anaspid dermal skeleton is composed of odontodes comprising spheritic dentine and enameloid, overlying a basal layer of acellular parallel fibre bone containing an extensive shallow canal network. A recoded and revised phylogenetic analysis using equal and implied weights parsimony resolves anaspids as monophyletic, nested among stem-gnathostomes. Our results suggest the anaspid dermal skeleton is a degenerate derivative of a histologically more complex ancestral vertebrate skeleton, rather than reflecting primitive simplicity. Hypotheses that anaspids are ancestral skeletonizing lampreys, or a derived lineage of jawless vertebrates with paired fins, are rejected.

Evolutionarily conserved phosphorylation and palmitoylation-dependent regulation of dopamine D1-like receptors in vertebrates

In the vertebrate central nervous system, dopamine is a neurotransmitter, acting as a modulator of variety of neuronal functions, including cognition, emotion, locomotor activity, hunger and satiety, and endocrine system regulation. Dopamine receptors are composed of D 1 , D 2 , D 3 , D 4 and D 5 receptors, which are classified into two major subtypes, D 1 -like (D 1 and D 5 ) and D 2 -like (D 2 , D 3 and D 4 ) dopamine receptors. D 1 -like receptors stimulate adenylyl cyclase (AC) activity, whereas D 2 -like receptors inhibit AC activity and these receptors modulate many signaling pathways in dopaminergic synapses. Previous studies showed that post-translational protein phosphorylation and palmitoylation of mammalian D 1 receptors regulate functional properties, stability, cellular localization and membrane trafficking of the receptors. Here, I further focus on conservation of phosphorylation and palmitoylation sites found in vertebrate and invertebrate D 1 -like receptor homologs. Analysis of databases provides evidence to suggest that PKA- and GRKs-catalyzed phosphorylation sites of D 1 -like receptors have been completely conserved in the vertebrate lineage, in spite of the divergence of D 1 -like receptors full-length amino acid sequences during molecular evolution. These intracellular phosphorylated serine and threonine residues of D 1 -like receptors are evolutionarily conserved against mutation pressure throughout vertebrate species with a couple of exceptions. Furthermore, a PKC-mediated phosphorylation site of D 1 -like receptors is conserved in gnathostomes (jawed vertebrates) and not exist in agnathans (jawless vertebrates). Another phosphorylation site for PKC has been additionally acquired only in mammalian D 1 receptor orthologs. These findings suggest that the multiple kinases-dependent regulation of dopaminergic synapses by phosphorylation is so critical for complex vertebrate higher brain function. Namely, dynamic regulation of dopaminergic synapses made possible by reversible phosphorylation of D1-like receptors may ensure the specific refined functions of vertebrate nervous systems. In contrast, broadly conserved palmitoylation sites in both vertebrate and invertebrate D 1 -like receptor homologs indicate that palmitoylated cysteines play crucial roles for sustaining the structural and functional regulations of D 1 -like receptors.

How Marine Isotope Stage 3 (MIS3) is reflected in northern Mesopotamia faunal assemblage of Argentina: The Xenarthra Cingulata case

MIS 3 (60–25 ka) corresponds to a long interstadial episode considered generally warmer than MIS 2 and 4, and including numerous and abrupt Dansgaard–Oeschger and Heinrich events, sometimes brief but very intense. The materials studied here, coming from the Late Pleistocene exposures in central-north Mesopotamia (Corrientes province, Argentina, Toropí/Yupoí Fm., MIS 3; ca. 52–36 ka), is characterized by the presence of a large and complex vertebrate assemblage, being the Cingulata (Xenarthra) one of the most frequently represented taxa. In this work we provide an updated list of cingulates from Corrientes province, referrable to the Late Pleistocene, after performing new collections in the area and revising previous determinations. This includes: a) Dasypodidae: Propraopus sulcatus Lund, Euphractus aff. Euphractus sexcinctus Linnaeus; Chaetophractus villosus (Desmarest); b) Pampatheriidae: Holmesina paulacoutoi (Cartelle-Guerra and Mahecha-Bohorquez), Pampatherium sp., Pampatherium typum Ameghino; c) Glyptodontidae: Panochthus tuberculatus (Owen), Panochthus sp., Glyptodon reticulatus Owen, Glyptodon sp., Neosclerocalyptus paskoensis (Zurita), Neosclerocalyptus cf. N. paskoensis (Zurita), Neosclerocalyptus sp. The paleoenvironmental context that may be inferred from the palaeofaunal, particularly from the diversity of cingulates in the Quaternary of Corrientes province, is characterized by alternating cold arid or semiarid pulses and warmer humid ones. Generating new evidence related to MIS 3. Even though the taxa recorded are not new, the relative occurrence of each one shows evident differences with those in other areas. Using this information, the diversity of cingulates is compared to that of Late Pleistocene faunas described for sediments from areas currently located in the provinces of Formosa and Buenos Aires (Argentina), northern Uruguay and southern Brazil. Lastly, palaeoclimatic and palaeobiogeographic aspects that may be inferred from the study of this assemblage are discussed in the context of the MIS 3.

Bone morphogenetic protein signaling promotes morphogenesis of blood vessels, wound epidermis, and actinotrichia during fin regeneration in zebrafish.

Zebrafish fin regeneration involves initial formation of the wound epidermis and the blastema, followed by tissue morphogenesis. The mechanisms coordinating differentiation of distinct tissues of the regenerate are poorly understood. Here, we applied pharmacologic and transgenic approaches to address the role of bone morphogenetic protein (BMP) signaling during fin restoration. To map the BMP transcriptional activity, we analyzed the expression of the evolutionarily conserved direct phospho-Smad1 target gene, id1, and its homologs id2a and id3. This analysis revealed the BMP activity in the distal blastema, wound epidermis, osteoblasts, and blood vessels of the regenerate. Blocking the BMP function with a selective chemical inhibitor of BMP type I receptors, DMH1, suppressed id1 and id3 expression and arrested regeneration after blastema formation. We identified several previously uncharacterized functions of BMP during fin regeneration. Specifically, BMP signaling is required for remodeling of plexus into structured blood vessels in the rapidly growing regenerate. It organizes the wound epithelium by triggering wnt5b expression and promoting Collagen XIV-A deposition into the basement membrane. BMP represents the first known signaling that induces actinotrichia formation in the regenerate. Our data reveal a multifaceted role of BMP for coordinated morphogenesis of distinct tissues during regeneration of a complex vertebrate appendage.

A Convergent and Essential Interneuron Pathway for Mauthner-Cell-Mediated Escapes

The Mauthner cell (M-cell) is a command-like neuron in teleost fish whose firing in response to aversive stimuli is correlated with short-latency escapes [1-3]. M-cells have been proposed as evolutionary ancestors of startle response neurons of the mammalian reticular formation [4], and studies of this circuit have uncovered important principles in neurobiology that generalize to more complex vertebrate models [3]. The main excitatory input was thought to originate from multisensory afferents synapsing directly onto the M-cell dendrites [3]. Here, we describe an additional, convergent pathway that is essential for the M-cell-mediated startle behavior in larval zebrafish. It is composed of excitatory interneurons called spiral fiber neurons, which project to the M-cell axon hillock. By invivo calcium imaging, we found that spiral fiber neurons are active in response to aversive stimuli capable of eliciting escapes. Like M-cell ablations, bilateral ablations of spiral fiber neurons largely eliminate short-latency escapes. Unilateral spiral fiber neuron ablations shift the directionality of escapes and indicate that spiral fiber neurons excite the M-cell in a lateralized manner. Their optogenetic activation increases the probability of short-latency escapes, supporting the notion that spiral fiber neurons help activate M-cell-mediated startle behavior. These results reveal that spiral fiber neurons are essential for the function of the M-cell in response to sensory cues and suggest that convergent excitatory inputs that differ in their input location and timing ensure reliable activation of the M-cell, a feedforward excitatory motif that may extend to other neural circuits.

Evolutionary Analysis of the B56 Gene Family of PP2A Regulatory Subunits.

Protein phosphatase 2A (PP2A) is an abundant serine/threonine phosphatase that functions as a tumor suppressor in numerous cell-cell signaling pathways, including Wnt, myc, and ras. The B56 subunit of PP2A regulates its activity, and is encoded by five genes in humans. B56 proteins share a central core domain, but have divergent amino- and carboxy-termini, which are thought to provide isoform specificity. We performed phylogenetic analyses to better understand the evolution of the B56 gene family. We found that B56 was present as a single gene in eukaryotes prior to the divergence of animals, fungi, protists, and plants, and that B56 gene duplication prior to the divergence of protostomes and deuterostomes led to the origin of two B56 subfamilies, B56αβε and B56γδ. Further duplications led to three B56αβε genes and two B56γδ in vertebrates. Several nonvertebrate B56 gene names are based on distinct vertebrate isoform names, and would best be renamed. B56 subfamily genes lack significant divergence within primitive chordates, but each became distinct in complex vertebrates. Two vertebrate lineages have undergone B56 gene loss, Xenopus and Aves. In Xenopus, B56δ function may be compensated for by an alternatively spliced transcript, B56δ/γ, encoding a B56δ-like amino-terminal region and a B56γ core.

A new heart for a new head in vertebrate cardiopharyngeal evolution.

It has been more than 30 years since the publication of the new head hypothesis, which proposed that the vertebrate head is an evolutionary novelty resulting from the emergence of neural crest and cranial placodes. Neural crest generates the skull and associated connective tissues, whereas placodes produce sensory organs. However, neither crest nor placodes produce head muscles, which are a crucial component of the complex vertebrate head. We discuss emerging evidence for a surprising link between the evolution of head muscles and chambered hearts - both systems arise from a common pool of mesoderm progenitor cells within the cardiopharyngeal field of vertebrate embryos. We consider the origin of this field in non-vertebrate chordates and its evolution in vertebrates.

Challenges posed by tick-borne rickettsiae: eco-epidemiology and public health implications.

Rickettsiae are obligately intracellular bacteria that are transmitted to vertebrates by a variety of arthropod vectors, primarily by fleas and ticks. Once transmitted or experimentally inoculated into susceptible mammals, some rickettsiae may cause febrile illness of different morbidity and mortality, and which can manifest with different types of exhanthems in humans. However, most rickettsiae circulate in diverse sylvatic or peridomestic reservoirs without having obvious impacts on their vertebrate hosts or affecting humans. We have analyzed the key features of tick-borne maintenance of rickettsiae, which may provide a deeper basis for understanding those complex invertebrate interactions and strategies that have permitted survival and circulation of divergent rickettsiae in nature. Rickettsiae are found in association with a wide range of hard and soft ticks, which feed on very different species of large and small animals. Maintenance of rickettsiae in these vector systems is driven by both vertical and horizontal transmission strategies, but some species of Rickettsia are also known to cause detrimental effects on their arthropod vectors. Contrary to common belief, the role of vertebrate animal hosts in maintenance of rickettsiae is very incompletely understood. Some clearly play only the essential role of providing a blood meal to the tick while other hosts may supply crucial supplemental functions for effective agent transmission by the vectors. This review summarizes the importance of some recent findings with known and new vectors that afford an improved understanding of the eco-epidemiology of rickettsiae; the public health implications of that information for rickettsial diseases are also described. Special attention is paid to the co-circulation of different species and genotypes of rickettsiae within the same endemic areas and how these observations may influence, correctly or incorrectly, trends, and conclusions drawn from the surveillance of rickettsial diseases in humans.

Social parasitism and the molecular basis of phenotypic evolution.

Contrasting phenotypes arise from similar genomes through a combination of losses, gains, co-option and modifications of inherited genomic material. Understanding the molecular basis of this phenotypic diversity is a fundamental challenge in modern evolutionary biology. Comparisons of the genes and their expression patterns underlying traits in closely related species offer an unrivaled opportunity to evaluate the extent to which genomic material is reorganized to produce novel traits. Advances in molecular methods now allow us to dissect the molecular machinery underlying phenotypic diversity in almost any organism, from single-celled entities to the most complex vertebrates. Here we discuss how comparisons of social parasites and their free-living hosts may provide unique insights into the molecular basis of phenotypic evolution. Social parasites evolve from a eusocial ancestor and are specialized to exploit the socially acquired resources of their closely-related eusocial host. Molecular comparisons of such species pairs can reveal how genomic material is re-organized in the loss of ancestral traits (i.e., of free-living traits in the parasites) and the gain of new ones (i.e., specialist traits required for a parasitic lifestyle). We define hypotheses on the molecular basis of phenotypes in the evolution of social parasitism and discuss their wider application in our understanding of the molecular basis of phenotypic diversity within the theoretical framework of phenotypic plasticity and shifting reaction norms. Currently there are no data available to test these hypotheses, and so we also provide some proof of concept data using the paper wasp social parasite/host system (Polistes sulcifer—Polistes dominula). This conceptual framework and first empirical data provide a spring-board for directing future genomic analyses on exploiting social parasites as a route to understanding the evolution of phenotypic specialization.

Carcass size shapes the structure and functioning of an African scavenging assemblage

The particle size of the food resource strongly determines the structure and dynamics of food webs. However, the ecological implications of carcass size variation for scavenging networks structure and functioning have been largely overlooked. Here we investigate differences in scavenging patterns due to carcass size in a complex vertebrate scavenger community, Hluhluwe‐iMfolozi Park, South Africa, while taking into account seasonality. We monitored the consumption of three types of experimental carcasses: ‘small’ (< 10 kg), ‘medium’ (10–100 kg) and ‘large’ (> 100 kg). We employed general lineal models to explore the influence of carcass size on 1) scavenging network structure (scavenger species richness per carcass) and 2) functioning (carcass detection time, consumption time, consumption rate and percentage of carrion consumed). We also tested whether the structure of the scavenging network of each carcass size was nested, i.e. whether the scavenging assemblage in species‐poor carcasses was a subset of the assemblage consuming species‐rich carcasses. We found strong evidence indicating that carcass size is a major factor governing the associated scavenger assemblage. Scavenger species richness per carcass and carcass consumption time and rate increased with carcass size, while carcass detection time and percentage of carrion biomass consumed were negatively related to carcass size. Strikingly, most of the carrion biomass was consumed by facultative scavengers, represented by large mammalian carnivores, rather than by obligate scavengers (i.e. vultures). Scavenging network nestedness tended to be higher at larger carcasses, and nestedness was sensitive to the removal of the most connected species in the network (spotted hyena) rather than vultures. When comparing scavenging and predation assemblages, crucial size‐dependent differences emerge. Also, we identified a traditionally ignored mechanism by which hunting large prey could be relatively less profitable for predators, namely the costs associated with competition from scavengers and decomposers.

Neuronal polarity: an evolutionary perspective.

Polarized distribution of signaling molecules to axons and dendrites facilitates directional information flow in complex vertebrate nervous systems. The topic we address here is when the key aspects of neuronal polarity evolved. All neurons have a central cell body with thin processes that extend from it to cover long distances, and they also all rely on voltage-gated ion channels to propagate signals along their length. The most familiar neurons, those in vertebrates, have additional cellular features that allow them to send directional signals efficiently. In these neurons, dendrites typically receive signals and axons send signals. It has been suggested that many of the distinct features of axons and dendrites, including the axon initial segment, are found only in vertebrates. However, it is now becoming clear that two key cytoskeletal features that underlie polarized sorting, a specialized region at the base of the axon and polarized microtubules, are found in invertebrate neurons as well. It thus seems likely that all bilaterians generate axons and dendrites in the same way. As a next step, it will be extremely interesting to determine whether the nerve nets of cnidarians and ctenophores also contain polarized neurons with true axons and dendrites, or whether polarity evolved in concert with the more centralized nervous systems found in bilaterians.

Phylostratigraphic profiles in zebrafish uncover chordate origins of the vertebrate brain.

An elaborated tripartite brain is considered one of the important innovations of vertebrates. Other extant chordate groups have a more basic brain organization. For instance, cephalochordates possess a relatively simple brain possibly homologous to the vertebrate forebrain and hindbrain, whereas tunicates display the tripartite organization, but without the specialized brain centers. The difference in anatomical complexity is even more pronounced if one compares chordates with other deuterostomes that have only a diffuse nerve net or alternatively a rather simple central nervous system. To gain a new perspective on the evolutionary roots of the complex vertebrate brain, we made here a phylostratigraphic analysis of gene expression patterns in the developing zebrafish (Danio rerio). The recovered adaptive landscape revealed three important periods in the evolutionary history of the zebrafish brain. The oldest period corresponds to preadaptive events in the first metazoans and the emergence of the nervous system at the metazoan–eumetazoan transition. The origin of chordates marks the next phase, where we found the overall strongest adaptive imprint in almost all analyzed brain regions. This finding supports the idea that the vertebrate brain evolved independently of the brains within the protostome lineage. Finally, at the origin of vertebrates we detected a pronounced signal coming from the dorsal telencephalon, in agreement with classical theories that consider this part of the cerebrum a genuine vertebrate innovation. Taken together, these results reveal a stepwise adaptive history of the vertebrate brain where most of its extant organization was already present in the chordate ancestor.

A dsRNA-binding protein of a complex invertebrate DNA virus suppresses the Drosophila RNAi response.

Invertebrate RNA viruses are targets of the host RNA interference (RNAi) pathway, which limits virus infection by degrading viral RNA substrates. Several insect RNA viruses encode suppressor proteins to counteract this antiviral response. We recently demonstrated that the dsDNA virus Invertebrate iridescent virus 6 (IIV-6) induces an RNAi response in Drosophila. Here, we show that RNAi is suppressed in IIV-6-infected cells and we mapped RNAi suppressor activity to the viral protein 340R. Using biochemical assays, we reveal that 340R binds long dsRNA and prevents Dicer-2-mediated processing of long dsRNA into small interfering RNAs (siRNAs). We demonstrate that 340R additionally binds siRNAs and inhibits siRNA loading into the RNA-induced silencing complex. Finally, we show that 340R is able to rescue a Flock House virus replicon that lacks its viral suppressor of RNAi. Together, our findings indicate that, in analogy to RNA viruses, DNA viruses antagonize the antiviral RNAi response.

Humanized HLA-DR4.RagKO.IL2RγcKO.NOD (DRAG) mice sustain the complex vertebrate life cycle of Plasmodium falciparum malaria.

BackgroundMalaria is a deadly infectious disease affecting millions of people in tropical and sub-tropical countries. Among the five species of Plasmodium parasites that infect humans, Plasmodium falciparum accounts for the highest morbidity and mortality associated with malaria. Since humans are the only natural hosts for P. falciparum, the lack of convenient animal models has hindered the understanding of disease pathogenesis and prompted the need of testing anti-malarial drugs and vaccines directly in human trials. Humanized mice hosting human cells represent new pre-clinical models for infectious diseases that affect only humans. In this study, the ability of human-immune-system humanized HLA-DR4.RagKO.IL2RγcKO.NOD (DRAG) mice to sustain infection with P. falciparum was explored.MethodsFour week-old DRAG mice were infused with HLA-matched human haematopoietic stem cells (HSC) and examined for reconstitution of human liver cells and erythrocytes. Upon challenge with infectious P. falciparum sporozoites (NF54 strain) humanized DRAG mice were examined for liver stage infection, blood stage infection, and transmission to Anopheles stephensi mosquitoes.ResultsHumanized DRAG mice reconstituted human hepatocytes, Kupffer cells, liver endothelial cells, and erythrocytes. Upon intravenous challenge with P. falciparum sporozoites, DRAG mice sustained liver to blood stage infection (average 3–5 parasites/microlitre blood) and allowed transmission to An. stephensi mosquitoes. Infected DRAG mice elicited antibody and cellular responses to the blood stage parasites and self-cured the infection by day 45 post-challenge.ConclusionsDRAG mice represent the first human-immune-system humanized mouse model that sustains the complex vertebrate life cycle of P. falciparum without the need of exogenous injection of human hepatocytes/erythrocytes or P. falciparum parasite adaptation. The ability of DRAG mice to elicit specific human immune responses to P. falciparum parasites may help deciphering immune correlates of protection and to identify protective malaria antigens.

The crayfish that was afraid of the light

Comparative Behavior We tend to assume that complex emotions, such as anxiety, only occur in mammals or other cognitively complex vertebrates. But a heightened sense of awareness and the avoidance of novel or dangerous environments could be helpful for any animal species. Fossat et al. show that crayfish exposed to a stressful electric field refuse to enter light arms in a light/dark maze, even after the electric field has been removed. The animals calmed down when they were injected with an anxiolytic drug used to treat anxiety in humans, and they entered the light as normal. The stressed animals had increased levels of the neurotransmitter serotonin in the brain, and injections of serotonin induced anxiety-like behavior in control animals. Thus, these invertebrates display a primitive form of anxiety that shares a mechanism with the more complex emotions displayed by vertebrates. Science , this issue p. [1293][1] [1]: /lookup/doi/10.1126/science.1248811

Aquatic invertebrate communities in tank bromeliads: how well do classic ecological patterns apply?

Tank bromeliads (Bromeliaceae) often occur in high densities in the Neotropics and represent a key freshwater habitat in montane forests, housing quite complex invertebrate communities. We tested the extent to which there are species richness–altitude, richness–environment, richness–size, richness–habitat complexity and richness–isolation relationships for the aquatic invertebrate communities from 157 bromeliads in Cusuco National Park, Honduras. We found that invertebrate species richness and abundance correlated most strongly, and positively, with habitat size, which accounted for about a third of the variance in both. Apart from bromeliad size (equivalent of the species–area relationship), we found remarkably little evidence of classic biogeographic and ecological relationships with species richness in this system. Community composition correlated with altitude, bromeliad size and position, though less than 20% of the variation was accounted for by the tested variables. The turnover component of dissimilarity between the communities correlated with altitude, while the nestedness-resultant component was related to bromeliad size. The unexplained variance could reflect a large stochastic component in the system, associated with the ephemerality of the habitat patches (both the plants themselves and the fluctuations in their water content) and stochasticity due to the dispersal dynamics in the system. We conclude that there is a small contribution of classic biogeographic factors to the diversity and community composition of aquatic invertebrates communities in bromeliads. This may be due to the highly dynamic nature of this system, with small patch sizes and high emigration rates. The patterns may mostly be driven by factors affecting colonisation success.

Central and peripheral monosynaptic, polysynaptic and collaterals connectivity in the rat

Central and peripheral monosynaptic, polysynaptic and collaterals connectivity in the rat

The Vertebrate Strategy for Brain Evolution

In the study of Biologically Inspired Cognitive Architectures (BICA), relatively little attention has been paid to the evolutionary development of cognitive capabilities. There are two successful evolutionary strategies, i.e. resilient and cheap to reproduce individuals vs. more capable individuals that are necessarily expensive to reproduce. The vertebrate family is the prime example of the “evolve more capable individual” strategy. A sequence of increasingly complex and cognitively capable individuals has resulted from the vertebrate strategy. At the heart of the vertebrate strategy is a set of midbrain structures common to all vertebrates. The role of the core structures seems to be preparing the body for different classes of sensory-guided behaviors, while interactions among the core structures insure appropriate switching between behavior classes. More complex vertebrate brains evolved by adding new structures with feedback loops that link the new structure to the core structures and to sensory and motor processing components. A general rule for a new vertebrate structure is that it has to leave the core structures along the central midline of the brain intact, and that it cannot degrade functionality found in brains without the new structure. The evolution of two new capabilities critical to cognitive performance is discussed: the evolution from non-specific anticipation to specific prediction, and the evolution of simple combinations of landmarks into detailed models of familiar places.