Development and postnatal neurogenesis in the retina: a comparison between altricial and precocial bird species

The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons, the leading cause of irreversible blindness in humans. Throughout vertebrate phylogeny, the retina has two kinds of specialized niches of constitutive neurogenesis: the retinal progenitors located in the circumferential marginal zone and Müller glia. The proliferative activity in the retinal progenitors located in the circumferential marginal zone in precocial birds such as the chicken, the commonest bird model used in developmental and regenerative studies, is very low. This region adds only a few retinal cells to the peripheral edge of the retina during several months after hatching, but does not seem to be involved in retinal regeneration. Müller cells in the chicken retina are not proliferative under physiological conditions, but after acute damage some of them undergo a reprogramming event, dedifferentiating into retinal stem cells and generating new retinal neurons. Therefore, regenerative response after injury occurs with low efficiency in the precocial avian retina. In contrast, it has recently been shown that neurogenesis is intense in the retina of altricial birds at hatching. In particular, abundant proliferative activity is detected both in the circumferential marginal zone and in the outer half of the inner nuclear layer. Therefore, stem cell niches are very active in the retina of altricial birds. Although more extensive research is needed to assess the potential of proliferating cells in the adult retina of altricial birds, it emerges as an attractive model for studying different aspects of neurogenesis and neural regeneration in vertebrates.     

Postnatal ontogeny of cholecystokinin receptors in rat brain

The postnatal ontogeny of cholecystokinin receptors and cholecystokinin was determined in rat brain. The binding of cholecystokinin (CCK) to rat forebrain receptors was very low at 1-2 days of age, rose to a maximum at 12 days (Bmax = 31 fmol/mg protein, Kd = 1.47 nM), and declined to adult levels by 26 days (Bmax = 17 fmol/mg protein, Kd = 1.39 nM). In contrast, forebrain concentrations of CCK measured by radioimmunoassay rose monotonically through day 27. Possible implications of the transient developmental peak of CCK receptors are discussed.     

Early ontogeny of locomotor behaviour: a comparison between altricial and precocial animals

The focus of this review is to examine the physiological and behavioural differences between the early ontogeny of locomotion in precocial and altricial species. Both groups of animals are capable of performing alternating stepping movements upon birth or hatching, indicating that the basic elements underlying locomotor synergy are present prior to expression of mature overground gait. Nevertheless, the notable difference between precocial and altricial animals is the ability of the former to walk and run soon after birth or hatching. The weight of experimental evidence suggests that postural constraints play an important role in preventing early expression of locomotor behaviour in altricial species. Even some precocial animals, however, need time to develop sufficient stability and balance to walk as an adult. Therefore, components of locomotor behaviour involving the maintenance of equilibrium need a period of maturation in both precocial and altricial species, possibly requiring locomotor experience to become fully mature.     

Hippocampal maturation in the precocial murid rodent Acomys cahirinus

Growth rates in the dentate gyrus and hippocampus proper of the precocial murid Acomys cahirinus were examined by measuring age-related changes in laminar volume in 0-, 10-, 20-, and 60-day postpartum animals. A biphasic course of maturation was observed in both structures, with rapid expansion occurring in the first 10 postnatal days and more gradual growth thereafter. This pattern of growth resembles those reported for newborn altricial murids such as the laboratory mouse and rat. However, due to the large differences in the length of gestation between Acomys and the rat and mouse, quite different patterns emerge when the species are compared on the basis of postconception age, indicating that rates of neural maturation are not the same in altricial and precocial murids .     

Postnatal development of cholecystokinin (CCK) binding sites in the rat forebrain and midbrain: an autoradiographic study

The postnatal development of cholecystokinin (CCK) binding sites in the rat forebrain and midbrain was studied by in vitro receptor autoradiography. In the majority of structures, the densities of sites were low over the first week after birth, increased until the third week, and decreased over the fourth week to reach adult levels. However, both the rate of increase and the extent of the decrease varied in large proportions among structures. For instance, labeling in the neocortex underwent its largest increase from postnatal day 10, while this increase was already begun at day 7 in the paleocortex. On the other hand, over the fourth postnatal week, the densities could either remain roughly constant (cingulate cortex), slightly decrease (thalamic reticular nucleus), or even return to background levels (pyramidal layer of hippocampus). These different timetables may depend mostly on the differential growth of cells expressing the CCK receptor gene within the developing CNS. The absence of CCK binding sites in most of the regions during the early postnatal period precludes a major role of this peptide in the embryonic development of the rat brain. However, in some regions as the ventromedial hypothalamic nucleus, the endopyriform cortex or the medial nucleus of amygdala, 30-50% of the adult levels were already present at birth. Whether this observation reflects an earlier functional maturation of these structures or a direct participation of the corresponding CCK systems in their development remains to be established.     

A comparative study of mossy fiber distribution in the brain of the precocial Acomys cahirinus and of the altricial Rattus norvegicus: neuroanatomical bases and behavioral correlates

Acomys cahirinus, the spiny mouse, is the only precocial murid. Given the relatively advanced state of neural maturation at birth, this species is therefore of interest for comparative studies of brain and behavioural development. Previous work on this species has indicated that (i) hippocampal thickness (relative to body weight) is greater in adult Acomys than in rats and mice; (ii) the hippocampus appears laminated at birth, unlike that of related altricial species; (iii) the degree of olfactory bulb maturation at birth is greater in Acomys than in gerbils or rats. In the study reported, the distribution of hippocampal mossy fibers of Acomys was compared with that of Rattus norvegicus, in order to extend our earlier findings. In addition, the implied involvement of hippocampal mossy fibers in olfaction suggests a relation to our studies of exploratory behaviour in this species.     

Comparative study of the early postnatal chicken and pigeon brain. A Golgi-study of telencephalon and cerebellum

One-day- and four-week-old chicken and pigeon brains were studied in Golgi preparations. The maturational stage of telencephalon and cerebellum was compared in the two species. It was concluded that while the neurons (both projection and interneurons) of the chick brain showed a considerable maturity at one-day, after hatching, the pigeon brain of the same age appeared to be rather immature. An exception was the ventral telencephalic area (basal nucleus and olfactory tubercle). Findings correlate nicely with the functional performance of the brain areas studied in a precocial (chicken) and altricial (pigeon) species.     

Ontogenesis of multiple forms of monoamine oxidase in rat brain regions and liver

The postnatal development of total, type-A and type-B monoamine oxidase (MAO) in the brain stem, forebrain and cerebellum, determined with preferred substrates or selective inhibitors, were found to follow different patterns. In the brain regions, MAO-A activity reached adult levels in the brain stem first, followed by the forebrain and cerebellum, while MAO-B reached adult levels in these regions at about the same time and later in postnatal life. On the other hand, both MAO-A and B activities were almost fully developed in the newborn liver. Moreover, total and type-A, but not type-B, showed a caudal-to-rostral sequence of biochemical maturation in the brain. The spatiotemporal pattern of differentiation of type-A and type-B activities in the brain tends to support the classification of brain MAO into two distinct isoenzymic forms.     

Localization of cholecystokinin binding sites in the adult and developing Brazilian opossum brain

Cholecystokinin (CCK) is now recognized as one of the most abundant peptides in the mammalian central nervous system. We have previously used immunohistochemistry to localize CCK in the adult and developing Brazilian opossum brain. However, little is known about the distribution of CCK binding sites in the developing mammalian brain. Therefore, to further our knowledge of the sites of action for CCK during development, we initiated a series of studies to localize CCK binding sites in the adult and developing Brazilian opossum. This species was chosen because pups are born in a fetus-like state. Receptor autoradiography was performed on coronally sectioned brains of 1 to 60 day postnatal (PN) animals and adults with 125I-Bolton Hunter-CCK-8 as the radioligand. Binding is evident in the 1PN opossum brainstem and is observed in the developing forebrain by 5PN. Region-specific binding increases during development, and binding in the 35PN brain resembles the adult pattern. Binding is evident prior to the detection of CCK-like immunoreactivity in many areas. The facial motor nucleus is identifiable and exhibits high levels of binding in Brazilian opossum pups of 10 to 35 days of age. However, binding is undetectable in the facial motor nucleus of 45 and 60PN pups. In general, the binding patterns for CCK in the adult opossum resemble those of other mammals and likely mediate similar physiological functions. However, some cholecystokininergic pathways appear to be unique to neonatal mammals. © 1993 Wiley-Liss, Inc.     

A comparative study of myelination in precocial and altricial murid rodents

The development of myelin staining was compared in two closely related rodent species, the precocial Acomys cahirinus and altricial Rattus norvegicus. While the progression of myelin staining was similar in both species (motor tracts myelinated before sensory systems, which were followed by forebrain fiber systems), the timing of maturation differed considerably: (1) at the same postconception age (PC38) Rattus was substantially more mature than Acomys, suggesting a relatively earlier onset of myelination in Rattus; although (2) from PC38-PC45, Acomys exhibited much more rapid growth than Rattus, indicating divergence in the rate of myelination. Both species appeared to reach maturity at a common postconception age corresponding to the time of weaning (PC45).     

Expression, but failing maturation of procholecystokinin in cerebellum.

The cerebellum is the only region of the central nervous system which has been found to be devoid of cholecystokinin (CCK). The assays used, however, have been directed against the alpha-amidated C-terminus of fully processed CCK peptides. Using Northern blot analysis and a library of radioimmunoassays specific for different sequences of proCCK in combination with chromatography and enzyme cleavage, we have now examined the expression and processing of proCCK in fetal, neonatal and adult cerebellar tissue from man, pig and rat. In rat cerebellum CCK mRNA was present already in the fetal state. Two weeks after birth the concentrations declined. Also proCCK was found in significant concentrations in the fetal human and rat cerebellum (approximately 20 pmol/g); but already before birth the expression began to decrease towards low concentrations in adults. The adult porcine cerebellum contained 3.2 pmol proCCK and glycine-extended processing intermediates per gram (range less than 0.1-10.4 pmol/g), and 0.8 pmol carboxyamidated CCK per gram (range 0.1-4.1 pmol/g) varying in size from CCK-58 to CCK-5. For comparison, the adult porcine cerebral cortex contained 757 pmol carboxyamidated CCK/g, 20 pmol glycine-extended CCK/g and no proCCK. We conclude that cerebellum expresses proCCK with the highest level of expression in fetal life. In comparison with other regions of the brain, the maturation to transmitter-active, carboxyamidated CCK peptides is, however, attenuated in both fetal and adult cerebellar tissue.     

Postural development in rats

Mammals adopt a limited number of postures during their day-to-day activities. These stereotyped skeletal configurations are functionally adequate and limit the number of degrees of freedom to be controlled by the central nervous system. The temporal pattern of emergence of these configurations in altricial mammals is unknown. We therefore carried out an X-ray study in unrestrained rats from birth (P0) until postnatal day 23 (P23). The X-rays showed that many of the skeletal configurations described in adult rodents were already present at birth. By contrast, limb placement changed abruptly at around P10. These skeletal configurations, observed in anesthetized pups, required the maintenance of precise motor control. On the other hand, motor control continued to mature, as shown by progressive changes in resting posture and head movements from P0 to P23. We suggest that a few innate skeletal configurations provide the necessary frames of reference for the gradual construction of an adult motor repertoire in altricial mammals, such as the rat. The apparent absence of a requirement for external sensorial cues in the maturation of this repertoire may account for the maturation of postural and motor control in utero in precocial mammals (Muir et al., 2000 for a review on the locomotor behavior of altricial and precocial animals).     

A lead-associated nuclear protein which increases in maturing brain and in differentiating neuroblastoma 2A cells exposed to cyclic AMP-elevating agents.

The lead-associated nuclear protein, p32/6.3, increases significantly in the postnatally developing rat cerebral cortex (Egle and Shelton, J. Biol. Chem., 261 (1986) 2294-2298). In the present study, this increase has been identified with late development of the cerebral cortex or forebrain because p32/6.3 reached adult levels 10 to 14 days after birth in guinea pig (a precocial animal) and after hatching in chicken. Comparison with other developmental processes indicates that p32/6.3 reaches adult levels just before or during the period of synapse maturation. Thus p32/6.3 may prove useful as a biochemical indicator of nuclear maturation in this period. The developmental regulation of p32/6.3 was further studied in mouse neuroblastoma 2a (Nb2a) cells. In vitro induction of differentiation of Nb2a cells by serum withdrawal from the culture medium increased p32/6.3, implicating p32/6.3 with differentiating neurons. This association was further strengthened when treatment of the Nb2a cells for 24 h with dibutyryl cAMP (1-5 mM), papaverine (5-12.5 micrograms/ml) or 3-isobutyl-1-methylxanthine (IBMX; 50-250 microM) increased the abundance of p32/6.3 1.5- to 3-fold more than serum withdrawal alone. 8-Bromo-cAMP (2-4 mM), N6-benzoyl cAMP (4 mM) and forskolin (10 microM) also increased the abundance of p32/6.3 in Nb2a cells, arguing that cAMP is involved in p32/6.3 regulation. These results, in conjunction with the postnatal increase of p32/6.3 in cerebral cortex, suggest a relationship between p32/6.3 levels and neuronal maturation.     

Ontogeny of cholecystokinin-8-containing neuron system of the rat: an immunohistochemical analysis. I. Forebrain and upper brainstem

Ontogeny of the cholecystokinin-8 (CCK) neuron system in the forebrain and upper brainstem of the rat was investigated by means of indirect immunofluorescence. CCK cells and fibers first appeared in the developing ventral tegmental area and in the primordium of the medial forebrain bundle, respectively, at gestational day 15 (12-14-mm embryos). From that time, CCK cells appeared in various areas of the forebrain and upper brainstem until birth and reached the maximum content at postnatal day 10. After postnatal day 10, although CCK cells tended to decrease slightly in number, colchicine treatment in the adult rats brought out numerous CCK cells in the same areas. In contrast, although CCK fibers developed only slightly during the fetal period, marked development was seen after birth, particularly between postnatal days 5 and 10. After that time, as the rats grew, CCK fibers continued to increase in number and formed a meshwork of varying density in various areas of the forebrain and upper brainstem.     

Early histological maturation in the hippocampus of the guinea pig

The vesicular zinc-rich synaptic systems of the principal neurons of the hippocampus are well developed in newborn guinea pigs, a precocial species. In addition, alvear and fimbrial myelinated fibers as well as significant inhibitory interneurons (i.e. somatostatin, parvalbumin and opioid immunoreactive hippocampal interneurons) are also well developed. On the contrary, neither vesicular zinc synapses nor myelinated fibers nor the above mentioned immunoreactive interneurons are detectable in newborn specimens of other related altricial species such as rats or rabbits. These data suggest that early maturation of a highly integrative center related to cognitive map building such as the hippocampus is characteristic of precocial species.     

On the evolutionary significance of encephalization in some eutherian mammals: effects of adaptive radiation, domestication, and feralization

Allometries of the brain to body size relationship in eutherian mammals are examined in this study as they can be used for comparative analyses concerning encephalization. In contrast with some modern presentations of this issue, an older concept is revived and expanded through this author's current study. Three allometries with clearly different slopes are valid and lead to reliable results: interspecific, intraspecific, and ontogenetic allometries. Interspecific allometries follow lines with slope values of 0.56 or 0.63 for larger and smaller species, respectively, and characterize different average encephalization plateaus with rodents and lagomorphs generally more strongly encephalized compared to basal insectivores. Artiodactyls, perissodactyls and carnivores as a whole are again on a higher but rather similar plateau. Several species of carnivores have reached different encephalization levels with respect to their average plateau indicating diverse radiations. A phylogenetic brain size increase from fossil to recent radiations is also evident. Intraspecific allometries have slope values of about 0.25. These are of help in comparing brain sizes of ancestral species with their domesticated relatives. Domestication has generally led to a brain size decrease, but species on higher encephalization plateaus show this trend more strongly than species on a lower level of encephalization. Several brain parts and the sense organs also decrease in size during the domestication process, but vary arbitrarily and to different degrees. Ontogenetic growth allometries are species-specific, but are especially different between altricial and precocial mammals. A very steep 1st phase slope of highly encephalized species is particularly useful for understanding evolutionary and adaptive phenomena. Domesticated mammals that have become feral do not show an increase in brain size despite living many generations in wild habitats.     

Olfactory bulb organization and development in Monodelphis domestica (grey short-tailed opossum).

The olfactory bulbs of adult and developing Monodelphis domestica were examined with a number of techniques. Golgi, Nissl, and Timm stains as well as acetylcholinesterase histochemistry revealed a high degree of order within the adult bulb. All major cell classes characteristic of most mammalian species were observed. Tufted cells appeared to be restricted to the superficial portion of the external plexiform layer. Developing Monodelphis pups were examined with Nissl-stained semithin sections and with immunocytochemistry for tyrosine hydroxylase, microtubule-associated protein 2, vimentin, and glial fibrillary acidic protein. Newborn pups are extremely immature, with few postmitotic cells present in the forebrain. Considerable maturation occurs over the first four postnatal weeks, and by postnatal day 30, the bulb assumes an adult-like organization. The extreme immaturity of the bulb at birth, coupled with its strict organization, suggest that Monodelphis is a particularly appropriate species for experimental examinations of olfactory system development.     

Cholecystokinin peptides and receptor binding in Alzheimer's disease

Summary Cholecystokinin (CCK) is a peptide that can be found in the cerebral cortex in high concentrations and is involved in learning and memory as well as neurodegenerative processes. Cortical brain samples from 9 patients with Alzheimer's disease and 9 matched control cases were studied with respect to the concentrations of various molecular forms of CCK and the CCK receptor binding characteristics. No differences were found between patients and controls in any of these measures. Significant correlations were found between the concentrations of CCK-8 sulphated and the three nonsulphated CCK peptides measured. In addition, the concentrations of CCK-4 and CCK-5 showed a highly significant and positive correlation.     

The evolution of cerebrotypes in birds

Multivariate analyses of brain composition in mammals, amphibians and fish have revealed the evolution of 'cerebrotypes' that reflect specific niches and/or clades. Here, we present the first demonstration of similar cerebrotypes in birds. Using principal component analysis and hierarchical clustering methods to analyze a data set of 67 species, we demonstrate that five main cerebrotypes can be recognized. One type is dominated by galliforms and pigeons, among other species, that all share relatively large brainstems, but can be further differentiated by the proportional size of the cerebellum and telencephalic regions. The second cerebrotype contains a range of species that all share relatively large cerebellar and small nidopallial volumes. A third type is composed of two species, the tawny frogmouth (Podargus strigoides) and an owl, both of which share extremely large Wulst volumes. Parrots and passerines, the principal members of the fourth group, possess much larger nidopallial, mesopallial and striatopallidal proportions than the other groups. The fifth cerebrotype contains species such as raptors and waterfowl that are not found at the extremes for any of the brain regions and could therefore be classified as 'generalist' brains. Overall, the clustering of species does not directly reflect the phylogenetic relationships among species, but there is a tendency for species within an order to clump together. There may also be a weak relationship between cerebrotype and developmental differences, but two of the main clusters contained species with both altricial and precocial developmental patterns. As a whole, the groupings do agree with behavioral and ecological similarities among species. Most notably, species that share similarities in locomotor behavior, mode of prey capture or cognitive ability are clustered together. The relationship between cerebrotype and behavior/ecology in birds suggests that future comparative studies of brain-behavior relationships will benefit from adopting a multivariate approach.     

Regional differences in the development of cholecystokinin-like activity in rat brain

The postnatal development of cholecystokinin (CCK) in rat brain was studied by radioimmunoassay and bioassay of tissue extracts. Marked differences were found in the patterns of development in different regions of the brain. In the cerebellum and brainstem of newborn rats the concentrations of CCK8-like immunoreactivity were 40-100% those in adults, whereas in more rostral regions the concentrations were 1-10% of those in adults. Between 0 and 14 days in concentrations of CCK-like activity measured by radioimmunoassay increased up to 30-fold in hypothalamus, cortex and olfactory bulb; in the cortex there were further increases up to 42 days. Cortical CCK was also measured by bioassay on rabbit gall bladder in vitro; bioactivity was identified in foetuses, and after birth showed a similar pattern of increase to that measured by radioimmunoassay. Immunoreactive material in extracts of neonatal cerebellum, brainstem and cortex was identified as CCK8 on the basis of cross-reactivity with different antisera, and chromatographic properties on gel filtration. The results raise the possibility of different rates of maturation of central CCKergic systems.