Barbara L. Finlay

Web-based method for translating neurodevelopment from laboratory species to humans

Biomedical researchers and medical professionals are regularly required to compare a vast quantity of neurodevelopmental literature obtained from an assortment of mammals whose brains grow at diverse rates, including fast developing experimental rodent species and slower developing humans. In this article, we introduce a database-driven website, which was created to address this problem using statistical-based algorithms to integrate hundreds of empirically derived developing neural events in 10 mammalian species (http://translatingtime.net/). The site, based on a statistical model that has evolved over the past decade, currently incorporates 102 different neurodevelopmental events obtained from 10 species: hamsters, mice, rats, rabbits, spiny mice, guinea pigs, ferrets, cats, rhesus monkeys, and humans. Data are arranged in a Structured Query Language database, which allows comparative brain development measured in postconception days to be converted and accessed in real time, using Hypertext Preprocessor language. Algorithms applied to the database also allow predictions for dates of specific neurodevelopmental events where empirical data are not available, including for the human embryo and fetus. By designing a web-based portal, we seek to make these comparative data readily available to all those who need to efficiently estimate the timing of neurodevelopmental events in the human fetus, laboratory species, or across several different species. In an effort to further refine and expand the applicability of this database, we include a mechanism to submit additional data.

Topography of visual and somatosensory projections to the superior colliculus of the golden hamster

The topography of visual and somatosensory projections to the superior colliculus in the Syrian hamster was studied using electrophysiological techniques. The visual projection to the superficial layers of the colliculus is similar in general topography to that described for other rodents. The magnification of the visual field on the colliculus surface was greatest for nasal visual field. The magnification factor paralleled retinal ganglion cell density for corresponding visual field sectors. In the deep layers of the colliculus, a somatosensory projection is found in register with the visual projection such that the anterior somatosensory field and nasalmost visual field are both represented in rostral colliculus; posterior somatosensory fields and temporal visual fields are found in caudal colliculus. Likewise, upper visual and somatosensory fields are found in medial colliculus, and lower visual and somatosensory fields are found in lateral colliculus. Large receptive fields make the somatosensory topography less precise than the visual topography, but this lack of precision could serve to keep the two maps generally in register during eye and body movements.

Regressive events in brain development and scenarios for vertebrate brain evolution

The problems of the evolution of varying brain size, the specialization of particular functional systems and overall differences in the relative complexity of brain organization are discussed in terms of alterations of regressive events in neurogenesis (cell death and axon retraction). Three scenarios for evolution, cascade reorganization, parcellation and heterochrony, are considered in light of regressive mechanisms during development.

The Limbic System in Mammalian Brain Evolution

Previous accounts of mammalian brain allometry have relied largely on data from primates, insectivores and bats. Here we examine scaling of brain structures in carnivores, ungulates, xenarthrans and sirenians, taxa chosen to maximize potential olfactory and limbic system variability. The data were compared to known scaling of the same structures in bats, insectivores and primates. Fundamental patterns in brain scaling were similar across all taxa. Marine mammals with reduced olfactory bulbs also had reduced limbic systems overall, particularly in those structures receiving direct olfactory input. In all species, a limbic factor with olfactory and non-olfactory components was observed. Primates, insectivores, ungulate and marine mammals collectively demonstrate an inverse relationship between isocortex and limbic volumes, but terrestrial carnivores have high relative volumes of both, and bats low relative volumes of both. We discuss developmental processes that may provide the mechanistic bases for understanding these findings.

A conserved pattern of brain scaling from sharks to primates

Several patterns of brain allometry previously observed in mammals have been found to hold for sharks and related taxa (chondrichthyans) as well. In each clade, the relative size of brain parts, with the notable exception of the olfactory bulbs, is highly predictable from the total brain size. Compared with total brain mass, each part scales with a characteristic slope, which is highest for the telencephalon and cerebellum. In addition, cerebellar foliation reflects both absolute and relative cerebellar size, in a manner analogous to mammalian cortical gyrification. This conserved pattern of brain scaling suggests that the fundamental brain plan that evolved in early vertebrates permits appropriate scaling in response to a range of factors, including phylogeny and ecology, where neural mass may be added and subtracted without compromising basic function.

Patterns of Vertebrate Neurogenesis and the Paths of Vertebrate Evolution

Any substantial change in brain size requires a change in the number of neurons and their supporting elements in the brain, which in turn requires an alteration in either the rate, or the duration of neurogenesis. The schedule of neurogenesis is surprisingly stable in mammalian brains, and increases in the duration of neurogenesis have predictable outcomes: late-generated structures become disproportionately large. The olfactory bulb and associated limbic structures may deviate in some species from this general brain enlargement: in the rhesus monkey, reduction of limbic system size appears to be produced by an advance in the onset of terminal neurogenesis in limbic system structures. Not only neurogenesis but also many other features of neural maturation such as process extension and retraction, follow the same schedule with the same predictability. Although the underlying order of event onset remains the same for all of the mammals we have yet studied, changes in overall rate of neural maturation distinguish related subclasses, such as marsupial and placental mammals, and changes in duration of neurodevelopment distinguish species within subclasses. A substantial part of the regularity of event sequence in neurogenesis can be related directly to the two dimensions of the neuraxis in a recently proposed prosomeric segmentation of the forebrain [Rubenstein et al., Science, 266: 578, 1994]. Both the spatial and temporal organization of development have been highly conserved in mammalian brain evolution, showing strong constraint on the types of brain adaptations possible. The neural mechanisms for integrative behaviors may become localized to those locations that have enough plasticity in neuron number to support them.

Neural development in metatherian and eutherian mammals: variation and constraint.

A model for predicting the timing of neurogenesis in mammals (Finlay and Darlington [1995] Science 268:1578–1584) is here extended to an additional five metatherian species and to a variety of other events in neural development. The timing of both the outgrowth of axonal processes and the establishment and segregation of connections proves to be as highly predictable as neurogenesis. Expressed on a logarithmic scale, late developmental events are as predictable as early ones. The fundamental order of events is the same in eutherian and metatherian animals, but there is a curvilinear relation between the event scales of the two; for metatherians, later events are slowed relative to earlier events. Furthermore, in metatherians, the timing of developmental events is more variable than in eutherians. The slowing of late developmental events in metatherians is associated with their considerably longer time to weaning compared with eutherians. J. Comp. Neurol. 411:359–368, 1999.

The role of the superior colliculus in visually guided locomotion and visual orienting in the hamster

Visually guided locomotion toward goal doors designated by various cues was assessed in normal hamsters, hamsters with undercuts of the superior colliculus, and hamsters with neonatal lesions of the superior colliculus. Scanning of visual arrays, orientation to novel stimuli, and orientation to sunflower seeds were assessed in the same animals. Collicular lesions produced no deficit in accuracy of choice of goal door, type of route taken, or speed of locomotion. By contrast, the same hamsters showed major deficits in spontaneous scan· ning and orientation to stimuli in the visual periphery. Hamsters with neonatal and adult collicular lesions performed identically on every task except orientation to sunflower seeds presented at various locations in the visual field; adult operates were somewhat more vari· able in their performance. The implications of these results for the concept of encephalization of function and the phylogeny of the optic tectum are discussed.

Short-term response variability of monkey striate neurons

Neurons in striate cortex appear to respond in a more variable manner to visual stimulation of their receptive fields than do retinal ganglion or lateral genicu-late nucleus (LGN) cells. The extent of this variability is of interest for both method-ological and theoretical reasons. Methodologically, it is valuable to know what number of samples taken over what period of time adequately assesses a cells response characteristics. Theoretically, some light may be shed on cortical connectivity by determining the relative variability of cell subgroups and the difference in variability between responses elicited by optimal and non-optimal stimuli. We obtained a measure of response variability for 333 neurons in striate cortex and for 16 neurons in the LGN. The data were collected from 46 monkeys (Macaca mulatta) in the standard acute preparation; they were paralyzed with Flaxedil and were artificially respired with 30 ~ O~-70 ~ N20. Only cells with receptive fields 2-5 ° from the fovea are included in this sample. The data collection and stimulus presentation system capable of producing visual stimuli in random order has been described elsewhere 5. Variability data were collected over the 3-4 rain period when the best orientation or length of an edge or bar was being assessed by sweeping a stimulus of optimal velocity across the receptive field using a waveform generator and a mirror galvanometer. All the impulses elicited during this sweep, which was typically 1 sec in duration per trial, were counted as the response. To obtain an index of variability the standard deviation of the response to 10 repeated presentations of a given stimulus was divided by the mean response and multiplied by 100. Low values indicate a cell with consistent responses and hence low variability; high values show high variability. Using a stimulus of optimal orientation, length, and velocity, the average index of variability for all units was 35.2 with a standard deviation of 20. Breakdowns of variability for simple (S-type) and complex (CX-type) cell groups appear in Fig. 1A. S-type cells are those oriented units which show spatially separated contrast specific subfields; CX-type cells are those oriented units which throughout their receptive fields respond to both light increment and light decrement 5. These categories correspond generally to Hubel and Wiesels a distinction between these two subgroups. Also included is a small sample of LGN units, studied in a similar manner, that had their receptive fields in the same part of …

Peripheral variability and central constancy in mammalian visual system evolution

Neural systems are necessarily the adaptive products of natural selection, but a neural system, dedicated to any particular function in a complex brain, may be composed of components that covary with functionally unrelated systems, owing to constraints beyond immediate functional requirements. Some studies support a modular or mosaic organization of the brain, whereas others emphasize coordination and covariation. To contrast these views, we have analysed the retina, striate cortex (V1) and extrastriate cortex (V2, V3, MT, etc.) in 30 mammals, examining the area of the neocortex and individual neocortical areas and the relative numbers of rods and cones. Controlling for brain size and species relatedness, the sizes of visual cortical areas (striate, extrastriate) within the brains of nocturnal and diurnal mammals are not statistically different from one another. The relative sizes of all cortical areas, visual, somatosensory and auditory, are best predicted by the total size of the neocortex. In the sensory periphery, the retina is clearly specialized for niche. New data on rod and cone numbers in various New World primates confirm that rod and cone complements of the retina vary substantially between nocturnal and diurnal species. Although peripheral specializations or receptor surfaces may be highly susceptible to niche-specific selection pressures, the areal divisions of the cerebral cortex are considerably more conservative.