The Independent Evolution of Dorsal Pallia in Multiple Vertebrate Lineages.

Comparative neurobiologists have long wondered when and how the dorsal pallium (e.g., mammalian neocortex) evolved. For the last 50 years, the most widely accepted answer has been that this structure was already present in the earliest vertebrates and, therefore, homologous between the major vertebrate lineages. One challenge for this hypothesis is that the olfactory bulbs project throughout most of the pallium in the most basal vertebrate lineages (notably lampreys, hagfishes, and lungfishes) but do not project to the putative dorsal pallia in teleosts, cartilaginous fishes, and amniotes (i.e., reptiles, birds, and mammals). To make sense of these data, one may hypothesize that a dorsal pallium existed in the earliest vertebrates and received extensive olfactory input, which was subsequently lost in several lineages. However, the dorsal pallium is notoriously difficult to delineate in many vertebrates, and its homology between the various lineages is often based on little more than its topology. Therefore, we suspect that dorsal pallia evolved independently in teleosts, cartilaginous fishes, and amniotes. We further hypothesize that the emergence of these dorsal pallia was accompanied by the phylogenetic restriction of olfactory projections to the pallium and the expansion of inputs from other sensory modalities. We do not deny that the earliest vertebrates may have possessed nonolfactory sensory inputs to some parts of the pallium, but such projections alone do not define a dorsal pallium.

Variation across Species and Levels: Implications for Model Species Research.

The selection of model species tends to involve two typically unstated assumptions, namely: (1) that the similarity between species decreases steadily with phylogenetic distance, and (2) that similarities are greater at lower levels of biological organization. The first assumption holds on average, but species similarities tend to decrease with the square root of divergence time, rather than linearly, and lineages with short generation times (which includes most model species) tend to diverge faster than average, making the decrease in similarity non-monotonic. The second assumption is more difficult to test. Comparative molecular research has traditionally emphasized species similarities over differences, whereas comparative research at higher levels of organization frequently highlights the species differences. However, advances in comparative genomics have brought to light a great variety of species differences, not just in gene regulation but also in protein coding genes. Particularly relevant are cases in which homologous high-level characters are based on non-homologous genes. This phenomenon of non-orthologous gene displacement, or "deep non-homology," indicates that species differences at the molecular level can be surprisingly large. Given these observations, it is not surprising that some findings obtained in model species do not generalize across species as well as researchers had hoped, even if the research is molecular.

Evolution of the hippocampus in reptiles and birds.

Although the hippocampus is structurally quite different among reptiles, birds, and mammals, its function in spatial memory is said to be highly conserved. This is surprising, given that structural differences generally reflect functional differences. Here I review this enigma in some detail, identifying several evolutionary changes in hippocampal cytoarchitecture and connectivity. I recognize a lepidosaurid pattern of hippocampal organization (in lizards, snakes, and the tuatara Sphenodon) that differs substantially from the pattern of organization observed in the turtle/archosaur lineage, which includes crocodilians and birds. Although individual subdivisions of the hippocampus are difficult to homologize between these two patterns, both lack a clear homolog of the mammalian dentate gyrus. The strictly trilaminar organization of the ancestral amniote hippocampus was gradually lost in the lineage leading to birds, and birds expanded the system of intrahippocampal axon collaterals, relative to turtles and lizards. These expanded collateral axon branches resemble the extensive collaterals in CA3 of the mammalian hippocampus but probably evolved independently of them. Additional examples of convergent evolution between birds and mammals are the loss of direct inputs to the hippocampus from the primary olfactory cortex and the general expansion of telencephalic regions that communicate reciprocally with the hippocampus. Given this structural convergence, it seems likely that some similarities in the function of the hippocampus between birds and mammals, notably its role in the ability to remember many different locations without extensive training, likewise evolved convergently. The currently available data do not allow for a strong test of this hypothesis, but the hypothesis itself suggests some promising new research directions.

Cortical folding: when, where, how, and why?

Why the cerebral cortex folds in some mammals but not in others has long fascinated and mystified neurobiologists. Over the past century-especially the past decade-researchers have used theory and experiment to support different folding mechanisms such as tissue buckling from mechanical stress, axon tethering, localized proliferation, and external constraints. In this review, we synthesize these mechanisms into a unifying framework and introduce a hitherto unappreciated mechanism, the radial intercalation of new neurons at the top of the cortical plate, as a likely proximate force for tangential expansion that then leads to cortical folding. The interplay between radial intercalation and various biasing factors, such as local variations in proliferation rate and connectivity, can explain the formation of both random and stereotypically positioned folds.

NSF workshop report: discovering general principles of nervous system organization by comparing brain maps across species.

Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene-structure-function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system 'maps' comprising molecular, anatomical, and physiological data. This research will identify which neural features are likely to generalize across species, and which are unlikely to be broadly conserved. It will also suggest causal relationships between genes, development, adult anatomy, physiology, and, ultimately, behavior. These causal hypotheses can then be tested experimentally. Finally, insights from comparative research can inspire and guide technological development. To promote this research agenda, we recommend that teams of investigators coalesce around specific research questions and select a set of 'reference species' to anchor their comparative analyses. These reference species should be chosen not just for practical advantages, but also with regard for their phylogenetic position, behavioral repertoire, well-annotated genome, or other strategic reasons. We envision that the nervous systems of these reference species will be mapped in more detail than those of other species. The collected data may range from the molecular to the behavioral, depending on the research question. To integrate across levels of analysis and across species, standards for data collection, annotation, archiving, and distribution must be developed and respected. To that end, it will help to form networks or consortia of researchers and centers for science, technology, and education that focus on organized data collection, distribution, and training. These activities could be supported, at least in part, through existing mechanisms at NSF, NIH, and other agencies. It will also be important to develop new integrated software and database systems for cross-species data analyses. Multidisciplinary efforts to develop such analytical tools should be supported financially. Finally, training opportunities should be created to stimulate multidisciplinary, integrative research into brain structure, function, and evolution.

NSF workshop report: discovering general principles of nervous system organization by comparing brain maps across species.

Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene-structure-function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system 'maps' comprising molecular, anatomical, and physiological data. This research will identify which neural features are likely to generalize across species, and which are unlikely to be broadly conserved. It will also suggest causal relationships between genes, development, adult anatomy, physiology, and, ultimately, behavior. These causal hypotheses can then be tested experimentally. Finally, insights from comparative research can inspire and guide technological development. To promote this research agenda, we recommend that teams of investigators coalesce around specific research questions and select a set of 'reference species' to anchor their comparative analyses. These reference species should be chosen not just for practical advantages, but also with regard for their phylogenetic position, behavioral repertoire, well-annotated genome, or other strategic reasons. We envision that the nervous systems of these reference species will be mapped in more detail than those of other species. The collected data may range from the molecular to the behavioral, depending on the research question. To integrate across levels of analysis and across species, standards for data collection, annotation, archiving, and distribution must be developed and respected. To that end, it will help to form networks or consortia of researchers and centers for science, technology, and education that focus on organized data collection, distribution, and training. These activities could be supported, at least in part, through existing mechanisms at NSF, NIH, and other agencies. It will also be important to develop new integrated software and database systems for cross-species data analyses. Multidisciplinary efforts to develop such analytical tools should be supported financially. Finally, training opportunities should be created to stimulate multidisciplinary, integrative research into brain structure, function, and evolution.

FGF2 delays tectal neurogenesis, increases tectal cell numbers, and alters tectal lamination in embryonic chicks.

Intraventricular injections of the fibroblast growth factor 2 (FGF2) are known to increase the size of the optic tectum in embryonic chicks. Here we show that this increase in tectum size is due to a delay in tectal neurogenesis, which by definition extends the proliferation of tectal progenitors. Specifically, we use cumulative labeling with the thymidine analog EdU to demonstrate that FGF2 treatment on embryonic day 4 (ED4) reduces the proportion and absolute number of unlabeled cells in the rostroventral tectum when EdU infusions are begun on ED5, as one would expect if FGF2 retards tectal neurogenesis. We also examined FGF2's effect on neurogenesis in the caudodorsal tectum, which is born 2-3 days after the rostroventral tectum, by combining FGF2 treatment on ED4 with EDU infusions beginning on ED8. Again, FGF2 treatment reduced the proportion and number of EdU-negative (i.e., unlabeled) cells, consistent with a delay in neurogenesis. Collectively, these data indicate FGF2 in embryonic chicks delays neurogenesis throughout much of the tectum and continues to do so for several days after the FGF2 injection. One effect of this delay in neurogenesis is that tectal cell numbers more than double. In addition, tectal laminae that are born early in development become abnormally thin and cell-sparse after FGF2 treatment, whereas late-born layers remain unaffected. Combined with the results of prior work, these data indicate that FGF2 delays tectal neurogenesis and, thereby, triggers a cascade of changes in tectum size and morphology.

Bird brains and tool use: beyond instrumental conditioning.

Few displays of complex cognition are as intriguing as nonhuman tool use. Long thought to be unique to humans, evidence for tool use and manufacture has now been gathered in chimpanzees, dolphins, and elephants. Outside of mammals, tool use is most common in birds, especially in corvids and parrots. The present paper reviews the evidence for avian tool use, both in the wild and in laboratory settings. It also places this behavioral evidence in the context of longstanding debates about the kinds of mental processes nonhumans can perform. Descartes argued that animals are unable to think because they are soulless machines, incapable of flexible behavior. Later, as human machines became more sophisticated and psychologists discovered classical and instrumental conditioning, skepticism about animal thinking decreased. However, behaviors that involve more than simple conditioning continued to elicit skepticism, especially among behaviorists. Nonetheless, as reviewed here, strong behavioral data now indicate that tool use in some birds cannot be explained as resulting entirely from instrumental conditioning. The neural substrates of tool use in birds remain unclear, but the available data point mainly to the caudolateral nidopallium, which shares both functional and structural features with the mammalian prefrontal cortex. As more data on the neural mechanisms of complex cognition in birds accrue, skepticism about those mental capacities should continue to wane.

Expansion, folding, and abnormal lamination of the chick optic tectum after intraventricular injections of FGF2.

Comparative research has shown that evolutionary increases in brain region volumes often involve delays in neurogenesis. However, little is known about the influence of such changes on subsequent development. To get at this question, we injected FGF2--which delays cell cycle exit in mammalian neocortex--into the cerebral ventricles of chicks at embryonic day (ED) 4. This manipulation alters the development of the optic tectum dramatically. By ED7, the tectum of FGF2-treated birds is abnormally thin and has a reduced postmitotic layer, consistent with a delay in neurogenesis. FGF2 treatment also increases tectal volume and ventricular surface area, disturbs tectal lamination, and creates small discontinuities in the pia mater overlying the tectum. On ED12, the tectum is still larger in FGF2-treated embryos than in controls. However, lateral portions of the FGF2-treated tectum now exhibit volcano-like laminar disturbances that coincide with holes in the pia, and the caudomedial tectum exhibits prominent folds. To explain these observations, we propose that the tangential expansion of the ventricular surface in FGF2-treated tecta outpaces the expansion of the pial surface, creating abnormal mechanical stresses. Two alternative means of alleviating these stresses are tectal foliation and the formation of pial holes. The latter probably alter signaling gradients required for normal cell migration and may generate abnormal patterns of cerebrospinal fluid flow; both abnormalities would generate disturbances in tectal lamination. Overall, our findings suggest that evolutionary expansion of sheet-like, laminated brain regions requires a concomitant expansion of the pia mater.

Causes and consequences of expanded subventricular zones.

Primates have evolved an expanded isocortex relative to many other mammals. Parrots and songbirds have evolved an expanded telencephalon relative to many other birds. Previous work suggests that the expansion of the telencephalon in parrots and songbirds as well as the isocortex in primates is achieved, at least in part, by selectively delaying neurogenesis, expanding the subventricular zone (SVZ) and delaying maturation. The finding that similar developmental alterations in the spatial and temporal pattern of neurogenesis evolved together in these two distant lineages suggests that a single change in developmental mechanism might account for the expansion of the isocortex or telencephalon. We here review how uniformly lengthening developmental schedules may result in delays of neurogenesis, the expansion of the SVZ and delayed maturation. We propose that delays in neurogenesis may cause ventricular zone (VZ) cells to proliferate faster than the VZ can expand, which may force many proliferating cells to leave the VZ and form an expanded SVZ. Prolonged proliferation in the VZ and SVZ causes delays in neuronal maturation, which in turn may promote learning from conspecifics. Thus, we suggest that a single heterochronic change in developmental timing may orchestrate a variety of changes in the spatial and temporal pattern of proliferation, which has important behavioral consequences in adulthood.

Evo-devo and brain scaling: candidate developmental mechanisms for variation and constancy in vertebrate brain evolution.

Biologists have long been interested in both the regularities and the deviations in the relationship between brain, development, ecology, and behavior between taxa. We first examine some basic information about the observed ranges of fundamental changes in developmental parameters (i.e. neurogenesis timing, cell cycle rates, and gene expression patterns) between taxa. Next, we review what is known about the relative importance of different kinds of developmental mechanisms in producing brain change, focusing on mechanisms of segmentation, local and general features of neurogenesis, and cell cycle kinetics. We suggest that a limited set of developmental alterations of the vertebrate nervous system typically occur and that each kind of developmental change may entail unique anatomical, functional, and behavioral consequences for the organism. Thus, neuroecologists who posit a direct mapping of brain size to behavior should consider that not any change in brain anatomy is possible.

Developmental Modes and Developmental Mechanisms can Channel Brain Evolution.

Anseriform birds (ducks and geese) as well as parrots and songbirds have evolved a disproportionately enlarged telencephalon compared with many other birds. However, parrots and songbirds differ from anseriform birds in their mode of development. Whereas ducks and geese are precocial (e.g., hatchlings feed on their own), parrots and songbirds are altricial (e.g., hatchlings are fed by their parents). We here consider how developmental modes may limit and facilitate specific changes in the mechanisms of brain development. We suggest that altriciality facilitates the evolution of telencephalic expansion by delaying telencephalic neurogenesis. We further hypothesize that delays in telencephalic neurogenesis generate delays in telencephalic maturation, which in turn foster neural adaptations that facilitate learning. Specifically, we propose that delaying telencephalic neurogenesis was a prerequisite for the evolution of neural circuits that allow parrots and songbirds to produce learned vocalizations. Overall, we argue that developmental modes have influenced how some lineages of birds increased the size of their telencephalon and that this, in turn, has influenced subsequent changes in brain circuits and behavior.

Species differences in early patterning of the avian brain.

The telencephalon is proportionately larger in parrots than in galliformes (chicken-like birds), whereas the midbrain tectum is proportionately smaller. We here test the hypothesis that the adult species difference in midbrain proportion is due to an evolutionary change in early brain patterning. In particular, we compare the size of the early embryonic midbrain between parakeets (Melopsittacus undulatus) and bobwhite quail (Colinus virgianus) by examining the expression domains of transcription factors Pax6 and Gbx2, which are expressed in the forebrain and hindbrain, respectively. Because these expression domains form rostral and caudal borders with the presumptive midbrain when this region is specified (Hamburger-Hamilton stages 9-11), they allow us to measure and compare the sizes of a molecularly defined presumptive midbrain in the two species. Based on published data from older embryos, we predicted that the molecularly defined midbrain territory is significantly larger in quail than parakeets. Indeed, our data show that normalized midbrain length is 33% greater in quail and that the midbrain to forebrain ratio is 28% greater. This is strong evidence of a significant species difference in early brain patterning.

Bigger brains cycle faster before neurogenesis begins: a comparison of brain development between chickens and bobwhite quail.

The chicken brain is more than twice as big as the bobwhite quail brain in adulthood. To determine how this species difference in brain size emerges during development, we examined whether differences in neurogenesis timing or cell cycle rates account for the disparity in brain size between chickens and quail. Specifically, we examined the timing of neural events (e.g. neurogenesis onset) from Nissl-stained sections of chicken and quail embryos. We estimated brain cell cycle rates using cumulative bromodeoxyuridine labelling in chickens and quail at embryonic day (ED) 2 and at ED5. We report that the timing of neural events is highly conserved between chickens and quail, once time is expressed as a percentage of overall incubation period. In absolute time, neurogenesis begins earlier in chickens than in quail. Therefore, neural event timing cannot account for the expansion of the chicken brain relative to the quail brain. Cell cycle rates are also similar between the two species at ED5. However, at ED2, before neurogenesis onset, brain cells cycle faster in chickens than in quail. These data indicate that chickens have a larger brain than bobwhite quail mainly because of species differences in cell cycle rates during early stages of embryonic development.

Phylogenetic origins of early alterations in brain region proportions.

Adult galliform birds (e.g. chickens) exhibit a relatively small telencephalon and a proportionately large optic tectum compared with parrots and songbirds. We previously examined the embryonic origins of these adult species differences and found that the optic tectum is larger in quail than in parakeets and songbirds at early stages of development, prior to tectal neurogenesis onset. The aim of this study was to determine whether a proportionately large presumptive tectum is a primitive condition within birds or a derived feature of quail and other galliform birds. To this end, we examined embryonic brains of several avian species (emus, parrots, songbirds, waterfowl, galliform birds), reptiles (3 lizard species, alligators, turtles) and a monotreme (platypuses). Brain region volumes were estimated from serial Nissl-stained sections. We found that the embryos of galliform birds and lizards exhibit a proportionally larger presumptive tectum than all the other examined species. The presumptive tectum of the platypus is unusually small. The most parsimonious interpretation of these data is that the expanded embryonic tectum of lizards and galliform birds is a derived feature in both of these taxonomic groups.