Precocial Guinea Pig Research Articles

Comparative Milestones in Rodent and Human Postnatal Central Nervous System Development.

Within the substantially different time scales characterizing human and rodent brain development, key developmental processes are remarkably preserved. Shared processes include neurogenesis, myelination, synaptogenesis, and neuronal and synaptic pruning. In general, altricial rodents experience greater central nervous system (CNS) immaturity at birth and accelerated postnatal development compared to humans, in which protracted development of certain processes such as neocortical myelination and synaptic maturation extend into adulthood. Within this generalization, differences in developmental rates of various structures must be understood to accurately model human neurodevelopmental toxicity in rodents. Examples include greater postnatal neurogenesis in rodents, particularly within the dentate gyrus of rats, ongoing generation of neurons in the rodent olfactory bulb, differing time lines of neurotransmitter maturation, and differing time lines of cerebellar development. Comparisons are made to the precocial guinea pig and the long-lived naked mole rat, which, like primates, experiences more advanced CNS development at birth, with more protracted postnatal development. Methods to study various developmental processes are summarized using examples of comparative postnatal injury in humans and rodents.

Developmental Differences in Neocortex Neurogenesis and Maturation Between the Altricial Dwarf Rabbit and Precocial Guinea Pig.

Mammals are born on a precocial–altricial continuum. Altricial species produce helpless neonates with closed distant organs incapable of locomotion, whereas precocial species give birth to well-developed young that possess sophisticated sensory and locomotor capabilities. Previous studies suggest that distinct patterns of cortex development differ between precocial and altricial species. This study compares patterns of neocortex neurogenesis and maturation in the precocial guinea pig and altricial dwarf rabbit, both belonging to the taxon of Glires. We show that the principal order of neurodevelopmental events is preserved in the neocortex of both species. Moreover, we show that neurogenesis starts at a later postconceptional day and takes longer in absolute gestational days in the precocial than the altricial neocortex. Intriguingly, our data indicate that the dwarf rabbit neocortex contains a higher abundance of highly proliferative basal progenitors than the guinea pig, which might underlie its higher encephalization quotient, demonstrating that the amount of neuron production is determined by complex regulation of multiple factors. Furthermore, we show that the guinea pig neocortex exhibits a higher maturation status at birth, thus providing evidence for the notions that precocial species might have acquired the morphological machinery required to attain their high functional state at birth and that brain expansion in the precocial newborn is mainly due to prenatally initiating processes of gliogenesis and neuron differentiation instead of increased neurogenesis. Together, this study reveals important insights into the timing and cellular differences that regulate mammalian brain growth and maturation and provides a better understanding of the evolution of mammalian altriciality and presociality.

Vasopressin excites interneurons to suppress hippocampal network activity across a broad span of brain maturity at birth

During birth in mammals, a pronounced surge of fetal peripheral stress hormones takes place to promote survival in the transition to the extrauterine environment. However, it is not known whether the hormonal signaling involves central pathways with direct protective effects on the perinatal brain. Here, we show that arginine vasopressin specifically activates interneurons to suppress spontaneous network events in the perinatal hippocampus. Experiments done on the altricial rat and precocial guinea pig neonate demonstrated that the effect of vasopressin is not dependent on the level of maturation (depolarizing vs. hyperpolarizing) of postsynaptic GABAA receptor actions. Thus, the fetal mammalian brain is equipped with an evolutionarily conserved mechanism well-suited to suppress energetically expensive correlated network events under conditions of reduced oxygen supply at birth.

Brief exposure to the biological mother “potentiates” the isolation behavior of precocial Guinea pig pups

When isolated rat pups are briefly reunited with a lactating female, her subsequent removal leads to a dramatic increase in the emission of ultrasonic vocalizations, but not other behaviors. Whether this socially induced augmentation of isolation behavior (i.e., "potentiation") is characteristic only of altricial rodents is not known. Therefore, we examined precocial guinea pig pups in a potentiation paradigm. Ten-day-old guinea pigs were isolated in a test cage for 10 min, at which time they were then placed into a second cage for 5 min that either contained a companion or, for controls, was empty. Pups were then isolated again in the test cage for a second 10-min period. Control pups showed a significant reduction in vocalizing and locomotor activity from the first to second isolation period. Exposure to the biological mother prevented the decline in both behaviors (Experiment 1), whereas exposure to a familiar littermate (Experiment 2) had no effect, and exposure to an unfamiliar lactating female (Experiment 3) had only a minimal effect on locomotor activity. The results show that potentiation of isolation behaviors is not limited to altricial rodents, and suggest that specific characteristics of the effect (i.e., its magnitude, the specific behaviors affected, and the selectivity of the response to particular social partners) varies with the abilities and requirements of the young, as well as the behavioral ecology of the species in question.

Maternal food restriction delays weaning in the guinea pig, Cavia porcellus

In mammals, the duration of lactation varies much more than other life history parameters in relation to body mass, both within and between species. The causes of this variation are poorly understood and seem to result from varying conditions of mothers and young. We studied the effect of long-term maternal food restriction on litter mass at birth, duration of lactation and offspring development in the precocial guinea pig. Mild experimental food restriction during reproduction resulted in prolonged nursing behaviour of mothers. Evidence for a threshold mass at weaning was, however, equivocal. In the guinea pig, benefits of prolonged lactation prove hard to understand, because nutritional benefits are minor. Independently of maternal food regime, pups terminated suckling attempts several days after mothers ceased nursing behaviour. The time between the last nursing behaviour and the last suckling attempts was not longer in litters with higher need, that is, in litters of food-restricted females, than in litters of females fed ad libitum. Under food restriction, mothers maintained their own body mass, leading in pups to lower mass at birth, reduced postnatal growth and lower body mass at maturity. Guinea pig mothers appear to be selected to value their own condition more than that of a litter. We suggest that lengthening of the nursing period under poor conditions is a life history response primarily of precocial mammals.

EFFECTS OF LITTER SIZE ON THE ENERGETICS OF REPRODUCTION IN A HIGHLY PRECOCIAL RODENT, THE GUINEA PIG

Litter size strongly affects reproductive output and is therefore of central interest for the understanding of life-history evolution. I investigated the effect of variation in litter size (natural and manipulated) on the energetics of reproduction in the highly precocial guinea pig (Cavia porcellus). Unlike the situation in altricial species, increasing litter size in this precocial rodent influenced maternal performance (increase in litter mass and decrease in mass of individual offspring) as strongly during gestation (68 days) as during lactation (20 days). To cover the energy cost of offspring production, mothers increased their daily food intake. Their daily increase in metabolizable energy intake varied significantly with litter size during gestation but not during lactation. Instead, offspring in large litters consumed more solid food during lactation than did offspring in small litters. The efficiency of energy conversion into offspring production was not affected by litter size, neither during gestation nor during lactation. Furthermore, manipulation of litter size did not influence a mother's total energy cost of lactation. As a consequence, offspring in enlarged litters grew significantly slower than offspring in reduced litters despite similar body masses at birth and significantly greater consumption of solid food by nursing offspring in large litters. Results suggest that the effect of litter size on the energetics of reproduction in the precocial guinea pig differs from that of altricial rodents. Consequently, ecological implications of variation in litter size in the precocial guinea pig might also be very different to those in altricial species.

Endotoxin-challenges precocial neonates and iron changes.

In adult mammals fever is associated with the reduction of blood plasma iron level. Immature mammals, however, show either a decrease (precocial animals such as guinea pig neonates) or a lack of reduction (altricial animals such as human neonates) of plasma iron in response to endotoxin. In order to determine whether this difference is connected with maturity just after delivery, plasma iron concentration, hematocrit, body temperature and body mass were measured in rat pups injected with E. coli endotoxin in doses of 50 or 200 micrograms kg-1. Rat pups, like human neonates, are altricial animals. In 7-day-old rats injection of LPS led to a dose-dependent decrease in plasma iron level. The fall in plasma iron was accompanied by changes in body temperature and body mass. The results showed that plasma iron response to endotoxin in altricial rat neonates is similar to that observed in precocial guinea pig pups.

A descriptive analysis of nursing behavior in the guinea pig (Cavia porcellus).

Earlier studies have clarified the sequence and control of behavioral interactions during nursing in the rat. For comparison, we analyzed nursing behavior in the precocial guinea pig (Cavia porcellus). The behaviors of 6 dams with litters of 3 pups were videotaped under undisturbed conditions during both phases of the light-dark cycle and after reunion during the light phase on Days 1, 2, 3, 6, and 13 postpartum. More time was spent nursing in the light than in the dark and in the 1st week than on Day 13. Pup licking was not required for nipple attachment to occur even on Day 1. Dams displayed a crouched nursing posture accompanied by 120 s or more of body plus head immobility, similar to the crouched stance in the rat; body plus head immobility was rarely seen in females not in a crouched stance.

The relative time course of axonal loss from the optic nerve of the developing guinea pig is consistent with that of other mammals

The relative timing of a number of events during the development of the visual system has recently been suggested to be consistent across a number of mammalian species (Dreher & Robinson, 1988). Some conflicting reports, however, had suggested that the precocial guinea pig might represent an exception to the generalized scheme. A quantitative study was thus carried out on the development of the optic nerve and retina of the guinea pig. Consistent with the prediction of a stable relative time course of mammalian visual development, axons and growth cones were found in the optic stalk from the 24th postconceptional day (40% of the period from conception to eye opening--the cecal period), the peak number of axons was observed on the 32nd postconceptional day (56% of the cecal period), and the phase of rapid axonal loss extended to the 39th and 42nd postconceptional days (68-74% of the cecal period). The number of axons in the adult optic nerve (117,000) represented about 37% of the peak number of axons. Additional observations indicated that during development of the optic nerve the mean axonal diameter increased approximately threefold from 0.31 microns to 1.06 microns. As in other mammals studied so far, myelination was first noted after the period of rapid axonal loss and continued until in the adult 97% of axons were found to be myelinated. In the retina, the presence of pyknotic profiles in the ganglion cell layers extends throughout the periods of loss of the optic nerve axons. Finally, the presence of pyknotic profiles in the amacrine sublayer suggest that in the guinea pig, as in other mammalian species, there is a loss of displaced amacrine cells as well as ganglion cells from the ganglion cell layer.

Neonatal Gastrointestinal Growth and Function: Are They Regulated by Composition of Feeds?

The effects of natural suckling versus a cow's milk formula on gastrointestinal growth and mucosal function were measured in newborn guinea pigs during the first 8 days of postnatal life. Comparable growth was achieved between the two groups. Both feeds appeared to be a stimulus for the growth of the gastrointestinal tract and expression of disaccharidases, but not for mucosal growth. Formula feeding was associated with a diminished rate of lactase expression and an enhanced rate of maltase and sucrase expression suggesting that the effect of natural suckling is regulatory, acting to delay expression of an inherent ontogenic programme uncovered by formula feeding. These finding in the precocial guinea pig contrast with those in the altricial rat, and have implications for our understanding of the regulation of gastrointestinal development and effects of formula feeds, in other species, including man.

CHANGES IN JEJUNAL EPITHELIAL MORPHOLOGY & KINETICS DURING SUCKLING & WEANING IN THE CROWING GUINEA PIG

Weaning, the nutritional adaptation from milk to solid diet, demands changes in Cl function. We measured jejunal mucosal morphology and kinetics during suckling and weaning to determine if the marked changes seen in the altricial rat also occur in the precocial guinea pig (CP). 79 animals mere studied. Croups of at least 3 CPs aged 1,7,14,21 and 28 d were given IP colchicine at time 0, and killed at 20 to 30 min intervals. Tissue was taken 5 cm from the pylorus, fixed and bulk stained with Schiff reagent. Jejunal morphology was measured by microdissection and crypt cell production rate (CCPR) by a metaphase arrest technique. There was 40% decline in villus ht, from 986 μm to 618 μm (p<0.001), and 25% increase in crypt depth, from 148 μm to 199μm (p<0.01), during the first 2 wks. After an initial decline there was an increase in crypt: villus (C;V) ratio from 6.7 to 8.2, and in CCPR from 3.9 to 5.6 cells/crypt/hr from 14 d onwards (pz0.001). These changes represent a proliferative response of jejunal epithelium during the 3rd & 4th postnatal weeks, accounted for by increase in the depth and number of crypts, and CCPR, leading to increase in net villus influx. In contrast with the rat in which abrupt changes in epithelial morphology, function and kinetics occur around d 21 at the time of cessation of suckling, in the CP they are gradual and follow weaning by some days. The CP, which in many respects more closely resembles man than rat, is a more suitable animal model for our understanding of human Cl maturation and perinatal nutritional adaptation.

Changes in upper intestinal epithelial morphology and kinetics in the growing guinea pig.

Weaning, the process of intestinal adaptation from milk to solid diet, demands changes in gastrointestinal function. We aimed to measure upper intestinal mucosal morphology and cytokinetics during early life, to determine whether the marked changes seen at weaning in altricial species, such as rat and mouse also occur in the precocial guinea pig. A total of 79 animals was studied. Jejunal morphology was measured by microdissection and crypt cell production rate by a metaphase arrest technique in animals at 1, 7, 14, 21, and 28 days after birth. There was a 40% decline in villus height from 986 to 576 microns during the first 2 wk (p less than 0.001). Crypt depth increased by 25% from 148 to 199 microns (p less than 0.01). After an initial decline there was a significant increase in crypt:villus ratio from 6.7 to 8.2 (p less than 0.001), in crypt cell production rate from 3.9 to 5.6 cells/crypt/h (p less than 0.001), and net villus influx from 26.1 to 45.9 cells/villus/h (p less than 0.001) from 14 days onward. These proliferative changes were accounted for by an increase in the depth and number of crypts, and in crypt cell production rate, leading to an increase in net villus influx. In contrast with the rat and mouse they were gradual, occurred largely during the 3rd wk, and appeared to follow the cessation of breast feeding and commencement of solid food. It is suggested that the functional changes in the small intestine that occur during weaning in the guinea pig are neither due to rapid proliferation of a new epithelial cell population, nor precipitated by change in diet.

Ontogenesis of circadian sleep-wakefulness rhythms and developmental changes of sleep in the altricial rat and in the precocial guinea pig.

Ontogenesis of circadian sleep-wakefulness rhythms and other developmental changes of sleep were examined in the altricial rat and in the precocial guinea pig. Circadian sleep-wakefulness rhythms began to emerge on the 4th-4.5th week after birth in rats born and raised not only under light-dark (LD) 12:12 h lighting schedule but also under a constant light condition. Only ultradian rhythms were recognized in the rat up to 2.5-3.5 weeks after birth. Unlike the rat, the guinea pig did not develop significant diurnal and circadian sleep rhythms during the course of its growth. Sleep-wakefulness rhythms of the 1-week-old infant guinea pig were very similar to those of the adult. During the development of the altricial rat the periods of slow wave sleep (SWS) and paradoxical sleep (PS) cycles, and the amounts of SWS per day increased. On the other hand, the amounts of PS per day and the length of the PS episodes decreased. For the guinea pig, however, these parameters of sleep were apparently constant throughout development.

The partial-reinforcement extinction effect in 4–5-day-old guinea pigs

The partial-reinforcement extinction effect was demonstrated at 4–5 days of age in the precocial guinea pig and was related to the appearance of this effect at 12–14 days in the altricial rat. We suggest that the maturity of the septohippocampal system at birth in the guinea pig, relative to the immaturity of this system in the rat, is a possible basis for this difference.