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The International Society for Developmental Psychobiology annual meeting symposium: Impact of early life experiences on brain and behavioral development.

Decades of research in the area of developmental psychobiology have shown that early life experience alters behavioral and brain development, which canalizes development to suit different environments. Recent methodological advances have begun to identify the mechanisms by which early life experiences cause these diverse adult outcomes. Here we present four different research programs that demonstrate the intricacies of early environmental influences on behavioral and brain development in both pathological and normal development. First, an animal model of schizophrenia is presented that suggests prenatal immune stimulation influences the postpubertal emergence of psychosis-related behavior in mice. Second, we describe a research program on infant rats that demonstrates how early odor learning has unique characteristics due to the unique functioning of the infant limbic system. Third, we present work on the rodent Octodon degus, which shows that early paternal and/or maternal deprivation alters development of limbic system synaptic density that corresponds to heightened emotionality. Fourth, a juvenile model of stress is presented that suggests this developmental period is important in determining adulthood emotional well being. The approach of each research program is strikingly different, yet all succeed in delineating a specific aspect of early development and its effects on infant and adult outcome that expands our understanding of the developmental impact of infant experiences on emotional and limbic system development. Together, these research programs suggest that the developing organism's developmental trajectory is influenced by environmental factors beginning in the fetus and extending through adolescence, although the specific timing and nature of the environmental influence has unique impact on adult mental health.

Animals↗

Evolutionary transformations of chorioallantoic placental characters in rodentia with special reference to hystricognath species.

The aim of this paper is to reconstruct the evolution of chorioallantoic placental characters in Rodentia. The analysis is based on pre-existing hypotheses of rodent relationships and the tracing of character evolution. Data on 64 rodent species of 49 genera are derived from the literature. New results refer to the hystricognath species Petromus typicus A. Smith, 1831 and Octodon degus (Molina, 1782). This comprehensive analysis confirms that the stem species pattern of Rodentia is characterised by a haemochorial placenta which is divided horizontally. Inside the placental labyrinth, fetal vessels and their trophoblastic external border build up a network through which the maternal blood flows. The trophoblastic tissue is one-layered, syncytial and possess a considerable surface extension. Within Rodentia, evolutionary transformations occurred on the macroscopic as well as the fine structural level. The results suggest that the stem species of Hystricognathi underwent transformations only on the macroscopic level, i.e., forming a ring-shaped arrangement of placental regions with centrally situated maternal arteries and the acquisition of a subplacenta. By contrast, in Muridae the chorioallantoic placenta shows derived features only in regard to the fine structure of the labyrinth, i.e. the interhaemal membrane is modified in composition, and the fetal capillary endothelium is fenestrated. Geomyoidea underwent transformations on both levels. Macroscopically, their placenta is modified into a hillock shape. Microscopically, the interhaemal membrane is formed by the cytotrophoblast. In addition to the mentioned transformations, some aspects of other fetal membrane differentiation in Rodentia are briefly discussed.

Allantois↗

Relation of glucocorticosteroids and testosterone to the annual cycle of free-living degus in semiarid central Chile.

We investigated seasonal patterns of plasma glucocorticosteroids (GCs) in both sexes and testosterone (T) in males in relation to the annual cycle in central Chile of a natural population of the degu (Octodon degus), a caviomorph rodent. We wanted to find out which GCs are present in degus, whether their seasonal variation suggests suppressive or synergistic interrelationships with T, and whether seasonal variation in GC levels indicates a relationship with energy mobilization and demands of reproduction. Degus mated in late autumn, and female body mass increased in pregnancy and remained high during lactation and throughout spring. Over the subsequent period of summer drought both sexes declined to a minimal body mass before the next mating season. Cortisol appears to be the principal GC in degus. In fact cortisol levels were so high that the extremely low levels of corticosterone measured were probably largely due to the cross-reactivity of our corticosterone antiserum with cortisol. Titers of cortisol in females exceeded 1000 ng/ml at lactation in the spring of 2 years; cortisol declined greatly following lactation and during the summer and reached its lowest mean level of about 500 ng/ml at mating. Males were more difficult to capture than females and thus our sampling was limited, but male cortisol levels were similar to those of females during the times of year when we measured them. Male T levels remained within a low range all year, but at mating, when mean T was highest (0.16 ng/ml) and when most males had detectable T, degus showed their lowest cortisol levels. The minimal cortisol level of males during mating represents a possible suppressive effect of T, as described in other mammals. At the time of their spring emergence, 60% of juvenile males had detectable T levels comparable to those of adults, suggesting important organizational effects of T at that time in their maturation. Peak cortisol titers in both sexes were associated with lactation in females, when energy mobilization, production, and body mass were at their greatest.

Animals↗

Amino acid sequence from degu islet amyloid-derived insulin shows unique sequence characteristics.

The main protein of enriched and purified amyloid from Octodon degus pancreatic islets was identified as insulin. The material was reduced and alkylated and the A- and the B-chain were separated by reversed phase chromatography and subjected to Edman degradation and amino acid analysis. It was shown that the A-chain contains two additional C-terminal amino acid residues (i.e. a total of 23 residues) and that the B-chain has a deletion in the C-terminal part (i.e. a total of 29 residues). The obtained sequence follows: A-chain: GIVDQCCNNICTFNQLQNYCNVP B-chain: YSSQHLCGSNLVEALYMTCGRSGFYRPHD.

Amino Acid Sequence↗

The pancreas in the degu.

Unique alpha-cell crystals, a herpes-like virus, islet amyloidosis, and immunohistochemical reactions of islets are compared in the rodent, Octodon degus, in animals with ordinary and high circulating glucose levels. Results suggest that crystals, virus, and amyloid are independent of blood sugar and bear no obvious relation to one another, although each is more common in older than in young animals. The crystals do not react with anti-glucagon. In the presence of high blood glucose, qualitative histochemical studies demonstrated diminished islet insulin and an unusual reaction with anti-somatostatin: (1) paucity of the usual cells that stain darkly for somatostatin and (2) striking staining of intermediate hue in most islet cells and in (3) multitudes of cell nests in exocrine parenchyma. The intermediate staining reaction may represent a visible demonstration of the paracrine phenomenon.

Amyloid↗

Isozyme heterogeneity and numerical taxonomy of Trypanosoma cruzi stocks from Chile.

Fifty-three stocks of Trypanosoma cruzi were isolated in Chile, 13 from patients, 32 from the domestic triatomine vector Triatoma infestans, and 8 from the silvatic and peridomestic vector T. spinolai. The majority of isolates from triatomine bugs were made by the direct culture of infected faeces. The 53 stocks and a single clone were characterized by a combination of starch-gel and cellulose acetate enzyme electrophoresis. Three groups of T. cruzi stocks were apparent from either simple visual comparisons of isozyme profiles or numerical taxonomy. The groups were designated Chilean zymodeme (Z) 1, which was similar to Brazilian Z1, Chilean Z2a, similar to Brazilian Z2 and Chilean Z2b, similar to Bolivian Z2 and with prominent heterozygous isozyme profiles. Chilean Z1 was isolated only from T. spinolai colonizing farm walls inhabited by the rodent Octodon degus. Chilean Z2a and Z2b were both isolated from domestic T. infestans T. infestans and man, in some cases within the same household. Hardy-Weinberg equilibria were not found amongst a group of 22 stocks from a single locality and deviations from theoretical Hardy-Weinberg distributions were compatible with the absence of genetic exchange in the sampled population of T. cruzi.

Alanine Transaminase↗

Species differences in the localization of neuropeptide FF receptors in rodent and lagomorph brain and spinal cord.

Quantitative in vitro receptor autoradiography of [125I][D-Tyr1,(NMe)Phe3]NPFF was used to study the regional distribution of neuropeptide FF receptors in rodent and lagomorph brain. In rat, mouse, rabbit, and Afghan pika [125I][D-Tyr1,(NMe)Phe3]NPFF binding sites were enriched in the superficial layers of dorsal horn of the spinal cord and in parabrachial nucleus, central gray matter, hypothalamus, and reunions thalamic nucleus. In other neuroanatomical regions, important species differences in NPFF receptor patterns are observed. In marked contrast, the brain and the spinal cord of the Octodon degus are devoid of NPFF receptors. The present study shows that in different species regional variations in brain NPFF receptor binding occur.

Animals↗

Comparative water economy of sympatric rodents in a Chilean semi-arid habitat.

1. Water requirements, water balance components and dependence on exogenous water were estimated in four species of sympatric rodents inhabiting a Chilean semi-arid region. 2. A significant increase in free water drinking was observed in all rodents when the diet composition was changed from 14 to 20% protein. 3. Under water balance conditions the cricetid species (Phyllotis darwini, Oryzomys longicaudatus and Akodon olivaceus) showed 1.66 to 1.88 times the weight-specific daily water gain of Octodon degus. 4. In the three cricetid rodents, evaporation was the largest water loss component (2/3 to 3/4 of total loss), while in O. degus evaporative water loss amounted to only 38% of the total. 5. Survival time during water deprivation ranged from 13.4 days in O. degus to only 4 days in O. longicaudatus. 6. All water variables combined indicate that water dependence of O. longicaudatus greater than P. darwini greater than A. olivaceus greater than O. degus.

Animals↗

Common procedures in hedgehogs, prairie dogs, exotic rodents, and companion marsupials.

Nondomesticated species are commonly being kept as companion animals. These include the African pygmy hedgehog (Atelerix albi-ventris), the North American black-tailed prairie dog (Cynomys lu-dovicianus), and exotic rodents such as the degu (Octodon degus)and duprasi or fat-tailed gerbil (Pachyuromys duprasi). Common companion marsupials include the sugar glider (Petaurus breviceps),Bennett's or Tammar (Dama) wallabies (Macropus rufogriseus rufo-griseus and Macropus eugenii, respectively), the Brazilian or South American gray short-tailed opossum (Monodelphis domestica), and the North American Virginia opossum (Didelphis virginiana). Although many of these animals are now bred domestically and are fairly docile when human-raised, they are essentially wild animals and hence have strong instincts to hide illness and pain.

Animal Diseases↗

Molecular systematics of the South American caviomorph rodents: relationships among species and genera in the family Octodontidae.

Nucleotide sequences from mitochondrial (12S rRNA) and nuclear (growth hormone receptor) genes were used to investigate phylogenetic relationships among South American hystricognath rodents of the superfamily Octodontoidea, with special emphasis on the family Octodontidae. Relationships among most taxa were well resolved by a combined analysis of both genes, and the molecular phylogeny was used to address several long-standing phylogenetic problems. The family Abrocomidae was the most basal lineage within the superfamily Octodontoidea, sensu stricto, and the family Ctenomyidae was sister to the family Octodontidae, followed by a monophyletic group containing the families Myocastoridae and Echimyidae. A basic dichotomy was observed within the family Octodontidae. The Argentine desert specialists, Tympanoctomys and Octomys, grouped separate from Octodontomys, which was sister to a clade containing a monophyletic Octodon and a clade represented by species of Aconaemys and Spalacopus. Aconaemys was paraphyletic relative to Spalacopus. The phylogeny was used as an interpretive framework for an examination of variation in several non-molecular characters. The primitive diploid number for most of the octodontoids was determined to be between 46 and 56, and the primitive genome size 8.2 pg. Members of the Octodontidae appeared to be derived from an ancestral stock occupying lower elevations in scrub habitat. Furthermore, estimates of divergence time from the molecular data provided a temporal perspective for changes in plant communities, which demonstrated turnover and diversification in response to climatic and geologic events occurring in the Miocene through the Pleistocene.

Animals↗

Test of the adaptive modulation hypothesis in rodents: dietary flexibility and enzyme plasticity.

The phenotypic response of digestive enzymes was assessed in two species of rodents with different foods habits. Species were Phyllotis darwini (omnivorous) and Octodon degus (herbivorous). The activity of sucrase, maltase and aminopeptidase-N were determined in vitro in animals feeding two contrasting diets. No effect of dietary chemistry on sucrase and maltase activities was observed. Nevertheless, aminopeptidase-N showed a reversible response to diet in P. darwini but not in O. degus. Through Principal Component Analysis we separated the specific and non-specific modulation of the enzymes. The analysis showed that aminopeptidase-N activity is up-regulated by dietary protein in P. darwini. Differences in the phenotypic response of this species apparently reflect the historic levels of specific substrates of the natural diets for this enzyme, linking dietary flexibility and digestive plasticity in an evolutionary context.

Adaptation, Physiological↗

Helminthoxys abrocomae n. sp. (Nematoda: oxyurida) from Abrocoma cinerea in Bolivia.

A new pinworm parasite is described from Abrocoma cinerea, a caviomorph rodent of the superfamily Octodontoidea from the Andes of Bolivia. The new species, Helminthoxys abrocomae n. sp., possesses special secretory mamelons which we consider a synapomorphy of the genus Helminthoxys. Within Helminthoxys, the closest relatives are found in octodontoid rodents: H. gigantea occurs in Octodon degus in Chile and O. bridgesi in Argentina, and H. freitasi is a parasite of Thrichomys aperoides in Brazil. H. abrocomae n. sp. differs from both other species morphometrically in relation to different parts of the body in both sexes, particularly the size of the body, spicule, gubernaculum and eggs, by the presence of a rough cuticular area around the cephalic sensory papillae and by the possession of very well-developed cervical alae which are strongly curved dorsally. H. abrocomae n. sp. is the tenth nominal species described in Helminthoxys, all of them being parasites of caviomorph rodents.

Animals↗

Number and nuclear localisation of nucleoli in mammalian spermatocytes.

In seven mammalian species, including man, the position and number of nucleoli in pachytene spermatocyte nuclei were studied from electron microscope (EM) nuclear sections or bivalent microspreads. The number and position of the nucleolar organiser regions (NORs) in mitotic and meiotic chromosomes were also analysed, using silver staining techniques and in situ hybridisation protocols. The general organisation of pachytene spermatocyte nucleoli was almost the same, with only minor morphological differences between species. The terminal NORs of Thylamys elegans (Didelphoidea, Marsupialia), Dromiciops gliroides (Microbiotheridae, Marsupialia), Phyllotys osgoodi (Rodentia, Muridae) and man, always gave rise to peripheral nucleoli in the spermatocyte nucleus. In turn, the intercalated NORs from Octodon degus, Ctenomys opimus (Rodentia, Octodontidae) and Chinchilla lanigera (Rodentia, Cavidae), gave rise to central nucleoli. In species with a single nucleolar bivalent, just one nucleolus is formed, while in those with multiple nucleolar bivalents a variable number of nucleoli are formed by association of different nucleolar bivalents or NORs that occupy the same nuclear peripheral space (Phyllotis and man). It can be concluded that the position of each nucleolus within the spermatocyte nucleus is mainly dependent upon: (1) the position of the NOR in the nucleolar bivalent synaptonemal complex (SC), (2) the nuclear pathway of the nucleolar bivalent SC, being both telomeric ends attached to the nuclear envelope, and (3) the association between nucleolar bivalents by means of their NOR-nucleolar domains that occupy the same nuclear space. Thus, the distribution of nucleoli within the nuclear space of spermatocytes is non-random and it is consistent with the existence of a species-specific meiotic nuclear architecture.

Animals↗

Angiotensin's contribution to dipsogenic additivity in several rodent species.

Significant positive correlations were obtained between plasma angiotensin levels and drinking following the administration of polyethylene glycol (PEG) in rats, gerbils, and hamsters and following isoproterenol (ISOP) in rats and gerbils, but not in a South American rodent, Octodon degus (degus). Hamsters revealed elevations in plasma angiotensin following ISOP but no drinking, whereas degus failed to show changes in plasma angiotensin to either treatment, although drinking occurred following PEG. All species drank to 2.5 M NaCl injections with no measurable changes in plasma angiotensin concentrations. A second experiment addressed our previous inability to measure [125I] angiotensin II (AII) specific binding in the brains of gerbils and degus and indicated that these animals possess circumventricular organ (CVO) angiotensin III (AIII) receptors; thus, circulating AIII may be the ligand in these species. A final experiment examined members of these species for dipsogenic additivity following the pairing of extracellular and intracellular thirst challenges. Rats and gerbils revealed additivity when challenged with either PEG or ISOP paired with 2.5 M NaCl. Degus and hamsters indicated additivity only with PEG and 2.5 M NaCl combined. Despite the presence of CVO angiotensin receptors in degus and hamsters, it is concluded that the important component of the hypovolemic dipsogenic stimulus in members of these species may be activation of volume receptors rather than brain angiotensin receptors.

Angiotensin II↗

Angiotensin III-induced dipsogenic and pressor responses in rodents.

Subcutaneous injections of [des-Asp1]-angiotensin I [( des-Asp1]-AI), angiotensin II (AII), and angiotensin III (AIII) induced drinking in the laboratory rat and the South American rodent Octodon degus, but not in the gerbil. In a second experiment, pretreatment with captopril, an angiotensin converting enzyme inhibitor, prevented the endogenous conversion of subcutaneously injected [des-Asp1]-AI to AIII and prevented drinking in rats and degus. The pharmacological artifact of hypovolemia caused by angiotensin-induced increases in vascular permeability was not observed in members of these species. In a final experiment blood pressure changes resulting from subcutaneous injections of AII and AIII in rats and gerbils were measured. Significant pressor elevations were seen following the administration of both analogues, although AII was more potent. These results demonstrate that AIII is dipsogenic in rats and degus and serves as a pressor agent in rats and gerbils. No ready explanation is available for the gerbil's relative lack of dipsogenicity to the presently tested angiotensins.

Angiotensin I↗

Juvenile emotional experience alters synaptic composition in the rodent cortex, hippocampus, and lateral amygdala.

A quantitative anatomical study in the rodent anterior cingulate and somatosensory cortex, hippocampus, and lateral amygdala revealed region-, cell-, and dendrite-specific changes of spine densities in 3-week-old Octodon degus after repeated parental separation. In parentally separated animals significantly higher spine densities were found on the apical and basal dendrites of the cingulate cortex (up to 143% on apical and 138% on basal dendrite). Branching order analysis revealed that this effect is seen on all segments of the apical dendrite, whereas on the basal dendrites significantly higher spine densities were seen only on the outer branches (third to fifth dendritic segments). Increased spine densities were also observed on the hippocampal CA1 pyramidal neurons (up to 109% on the distal apical segments and up to 106% on the basal segment) compared with the control group. In contrast, significantly reduced spine densities were observed on the granule cell dendrites in the dentate gyrus (down to 92%) and on the apical dendrites in the medial nucleus of the amygdala (down to 95%). No significant changes of spine densities were seen in the somatosensory cortex (except for an increase in the proximal apical segments) and in the lateral nucleus of the dorsal amygdala (except for an increase in the proximal basal dendritic segments). These results demonstrate that repeated stressful emotional experience alters the balance of presumably excitatory synaptic inputs of pyramidal neurons in the limbic system. Such experience-induced modulations of limbic circuits may determine psychosocial and cognitive capacities during later life.

Amygdala↗

Daily rhythms of food intake and feces reingestion in the degu, an herbivorous Chilean rodent: optimizing digestion through coprophagy.

Animals must match their foraging and digestion to seasonal changes in availability and quality of food. When these parameters decline, the animal's performance limits for extracting energy and nutrients may be challenged. In the laboratory, we investigated daily patterns of food processing on a low-quality (high-fiber) diet of alfalfa in an herbivorous, day-active rodent, the degu (Octodon degus), which inhabits semiarid central Chile. We manipulated timing of food availability, from continuous availability down to as little as 5 h/d. Degus maintained weight while digesting only 53% of dry-matter consumption. With food continuously available in a metabolic cage, the animals ate more food and deposited about twice as much feces in the day as at night. Continuous 24-h behavioral observation revealed that degus were actually defecating at the same rate both night and day but then ingesting most of the feces they produced at night. Further experimental treatments challenged animals with limited periods of food availability that matched natural foraging patterns. With either 11 h of daytime food availability or only 5 h (in morning and afternoon periods of 2.5 h each), degus consumed as much food as those with 24-h food availability. Continuous 24-h behavioral observations revealed in the 11-h group that nearly all feces produced at night were reingested and nearly none were reingested in the day, whereas the 5-h group resorted to further coprophagy during the 6-h midday interval with no food. Despite these differences in timing of food intake and coprophagy in response to the three experimental treatments, the degus were defecating at the same rate both night and day, which indicated a constant rate of output from the colon. This suggests a range of adjustments of digestive physiology to the timing of gut function by balancing coprophagy with ingestion of food. Overall, 38% of 24-h feces production was reingested, and 87% of this coprophagy occurred at night. The ingestion of feces during parts of the day when food is unavailable provides for continued intake into the digestive tract and appears to represent an increase in overall efficiency of gut use.

Animals↗

Juvenile emotional experience alters synaptic inputs on pyramidal neurons in the anterior cingulate cortex.

Analogous to the experience-driven development of sensory systems, the functional maturation of limbic circuits is significantly influenced by early socio-emotional experience. In a combined light and electron microscopic study in the anterior cingulate cortex of Octodon degus, the densities of spine and shaft synapses on apical dendrites of layer III pyramidal neurons were compared in 45 day old (1) undisturbed control animals; (2) handled animals; (3) animals which were repeatedly maternally deprived during the first three postnatal weeks; (4) animals which were treated similarly to group 3 and thereafter kept in chronic social isolation. Animals in groups 2-4 showed significantly higher spine densities (up to 121%, 142% and 151% respectively) compared to control group 1. Group 3 displayed significantly longer apical dendrites compared to control group 1. The electron microscopic analysis in cortical layer II revealed significantly higher spine synapses in group 4 (up to 166%) and fewer shaft synapses in groups 3 and 4 (down to 53% and 65% respectively) compared to group 1. These results demonstrate that early traumatic emotional experience alters synaptic input of pyramidal neurons. Such experience-induced modulation of limbic cortex development may determine psychosocial and cognitive capacities during later life.

Algorithms↗