Developmental continuity of working memory from infancy to preschool age

The objective of the paper was to study the developmental continuity of working memory function from infancy to preschool age. At the age of 10 to 11 months 44 participants completed delayed response task (A-not-B) that measures working memory function. Between 5 and 7 years of age the same participants performed three tasks assessing working memory for temporal order in auditory and visual modalities and a control task measuring short-term visuospatial memory. The dependence of temporal-order memory at preschool age on individual level of infant working memory was found for all methods of measurement despite the differences in way of presentation and reproducing of the stimuli order. Results indicate direct continuity in the development of working memory function from infancy to preschool age.     

Neural correlates of visual working memory: fMRI amplitude predicts task performance

We used fMRI to investigate how moment-to-moment neural activity contributes to success or failure on individual trials of a visual working memory (WM) task. We found that different nodes of a distributed cortical network were activated to a greater extent for correct compared to incorrect trials during stimulus encoding, memory maintenance during delays, and at test. A logistic regression analysis revealed that the fMRI signal amplitude during the delay interval in a network of frontoparietal regions predicted successful performance on a trial-by-trial basis. Differential delay activity occurred even for only those trials in which BOLD activity during encoding was strong, demonstrating that it was not a simple consequence of effective versus ineffective encoding. Our results indicate that accurate memory depends on strong sustained signals that span the delay interval of WM tasks.     

Does absolute brain size really predict self-control? Hand-tracking training improves performance on the A-not-B task

Large-scale, comparative cognition studies are set to revolutionize the way we investigate and understand the evolution of intelligence. However, the conclusions reached by such work have a key limitation: the cognitive tests themselves. If factors other than cognition can systematically affect the performance of a subset of animals on these tests, we risk drawing the wrong conclusions about how intelligence evolves. Here, we examined whether this is the case for the A-not-B task, recently used by MacLean and co-workers to study self-control among 36 different species. Non-primates performed poorly on this task; possibly because they have difficulty tracking the movements of a human demonstrator, and not because they lack self-control. To test this, we assessed the performance of New Caledonian crows on the A-not-B task before and after two types of training. New Caledonian crows trained to track rewards moved by a human demonstrator were more likely to pass the A-not-B test than birds trained on an unrelated choice task involving inhibitory control. Our findings demonstrate that overlooked task demands can affect performance on a cognitive task, and so bring into question MacLean''s conclusion that absolute brain size best predicts self-control.     

Age-associated changes in initiation of ribonucleic acid synthesis in isolated rat liver nuclei.

Initiation of RNA synthesis was studied in an attempt to determine a possible molecular mechanism for age-related biochemical and physiological changes. Initiation of RNA synthesis was determined by incorporation of [gamma-32 P]ATP and of [gamma-32P]GTP into an acid-insoluble product by intact nuclei isolated from livers of Sprague-Dawley CD-strain rats of various ages. When the rats were grouped into young (0.75-9 months) and old (12-30 months) rats, a significant decrease (P less than or equal to 0.001) in incorporation of initiating nucleotides was observed. The rat population was divided into five age groups (0.75-3 months, 4-9 months, 12-18 months, 19-23 months and 30 months) for further analysis of the effect of age on the initiation of RNA synthesis. Analysis of data from these groups indicated a significant trend for an age-related decrease in RNA-synthesis initiation (correlation coefficient = 0.94). Long-term hypophysectomy coupled with minimal hormone-replacement therapy was shown to have a significant effect on the reversal of the age-related decrease in initiation of RNA synthesis. It was observed that initiation of RNA synthesis in nuclei from 19-month-old rats, hypophysectomized at 12 months of age, was closest to that in 3-month-old intact rats and was not significantly different from that in liver nuclei of 0.75-9-month-old intact rats.     

Aging-related changes of EEG synchronization during a visual working memory task

Differences of EEG synchronization between normal old and young people during a working memory (WM) task were investigated. The synchronization likelihood (SL) is a novel method to assessed synchronization in multivariate time series for non-stationary systems. To evaluate this method to study the mechanisms of WM, we calculated the SL values in brain electrical activity for both resting state and task state. EEG signals were recorded from 14 young adults and 12 old adults during two different states, respectively. SL was used to measure EEG synchronization between 19 electrodes in delta, theta, alpha1, alpha2 and beta frequency bands. Bad task performance and significantly decreased EEG synchronization were found in old group compared to young group in alpha1, alpha2 and beta frequency bands during the WM task. Moreover, significantly decreased EEG synchronization in beta band in the elder was also detected during the resting state. The findings suggested that reduced EEG synchronization may be one of causes for WM capacity decline along with healthy aging.     

Differences in reversed plasmalemmal Na/Ca exchange activities among neuronal subtypes

The aging induces free radicals leading to DNA damage (8-oxo-2'-deoxyguanosine, 8-oxo2dG). DNA injury causes increased expression of p53 gene and p53 protein. Levels of 8-oxo2dG (HPLC), p53 mRNA (PCR) and p53 protein (Western blot) were estimated in gray matter (GM), white matter (WM), cerebellum (C) and medulla oblongata (MO) of control, 12- and 24-month-old rats. The level of 8-oxo2dG increased with age in C ( P  < 0.05 in 12-month-old and P  < 0.01 in 24-month-old rats) and MO. In 12-month-old animals the level of 8-oxo2dG in GM and WM was higher than in controls. In 12-month-old animals p53 gene expression decreased while amounts of p53 protein increased, depending on the oxidative DNA damage. In 24-month-old rats, expression of p53 increased in all structures ( P  ≤ 0.05) while p53 protein showed decreased levels in most of structures of central nervous system (WM, C, MO). Aging leads to increased 8-oxo2dG and augmented p53 gene expression, accompanied by a lowered expression of p53 protein.     

Adoption of an additional infant by a Western lowland gorilla (Gorilla gorilla gorilla).

A 10-year-old Western lowland gorilla, already caring for her own 14-month-old son, adopted a female neonate. The infant's mother (aged 7 years, 4 months) showed no interest in the infant, and it is unclear whether she abandoned the infant or whether it was seized by the dominant foster-mother. The foster-mother gave more maternal attention to the adoptee than to her own son but gave both infants the same protection. She adjusted her forms of transport to the age of each infant. The subadult mother of the neonate did not seek contact with her offspring during the first 4 weeks and in fact showed more interest in the 14-month-old male infant. Interactions between the two mothers were rare. The foster-mother's own male infant died 2 months after she had adopted the female infant. She looked after the adopted infant for 1 year, but then lost interest so that the adoptee had to be separated.     

Estrogen replacement enhances acquisition of a spatial memory task and reduces deficits associated with hippocampal muscarinic receptor inhibition

A delayed matching-to-position (DMP) T-maze task was used to examine the effects of estrogen replacement on spatial learning and memory, as well as the ability of estrogen replacement to reduce performance deficits produced by acute systemic and intrahippocampal muscarinic cholinergic inhibition. Two experiments were performed. In Experiment 1, ovariectomized animals were trained to criterion on the DMP task and then tested with increased intertrial delays and following systemic scopolamine administration. The animals then received either continuous estrogen replacement or sham surgery and were retested beginning 10 days later. In Experiment 2, ovariectomized animals received guide cannulae implanted bilaterally into the hippocampus. Half of these animals also began receiving continuous estrogen replacement. Two months later, the animals were trained on the DMP task and then tested with increased intertrial delays and following systemic as well as intrahippocampal scopolamine administration. Animals received the same test battery 8 months later and were then immediately trained on a reversal task. The results indicate that estrogen-treated animals acquired the DMP task at a significantly faster rate than the ovariectomized, non-estrogen-treated controls. In addition, estrogen replacement significantly reduced deficits in DMP performance produced by intrahippocampal, but not systemic, scopolamine administration. This occurred when animals were tested after 3.5 months, as well as after 12 months, of continuous estrogen replacement. No evidence for an effect of estrogen replacement on spatial working memory or reversal learning was detected. These findings demonstrate that estrogen replacement can enhance acquisition of a spatial memory task and reduce performance deficits associated with hippocampal cholinergic impairment.     

Pre- and postnatally administered ACTH, Organon 2766 and CRF facilitate or inhibit active avoidance task performance in young adult mice

This study investigated the effect of learning/memory-related neuropeptides on behavioral task performance in later life. A 1 mg/kg dosage of adrenocorticotropic hormone 4-9, Organon 2766, ACTH/MSH 4-10, ACTH 1-24, CRF, or diluent was subcutaneously injected into either pregnant females or into newborn pups during specific neural developmental windows. Each of the progeny was trained in an active-avoidance task and tested for acquisition on postpartum days 35-37. The mice were then tested for memory task performance and reacquisition on days 42-44 postpartum using the identical experimental paradigm as that used in the training sessions. Prenatal treatment with these memory-related neuropeptides resulted in significant facilitation of learning/memory task performance in male and female mice treated with Organon 2766 (p less than 0.001), and a significant inhibition of learning/memory task performance in males and females treated with ACTH 1-24 (p less than 0.01). Additional sex-specific performance facilitations and inhibitions resulted from the pre- or postnatal administration of the various neuropeptides used in this study. These results suggest that neuropeptides, when available in increased amounts during specific neural developmental windows, can significantly improve or suppress related behavioral performance capability in later life.     

Behavioral compensations in a positional learning and memory task by aged monkeys

The present experiment assessed learning and memory of a positional task by evaluating behavioral strategies as well as accuracy of a task in four young and four aged monkeys. They were tested in a delayed response (DR) task that has been widely used to study animal models of aging. The task consisted of two phases; an acquisition of the task and a positional memory test with five delay times (1-30 s). There was no clear difference between age groups in the number of trials needed for acquisition of the task. However, an analysis of behavior revealed differences in behavioral characteristics displayed during testing. The young monkeys showed various irrelevant behaviors during the execution of the task. In contrast, the aged monkeys consistently concentrated on the task exhibiting no behaviors irrelevant to the task. These results showed than the aged monkeys' performance was supported by a different behavioral strategy from the young monkeys. The results of the memory test were similar to those of the acquisition on the accuracy and the behavior. The aged monkeys depended on behavioral cues to preserve their positional memory, especially during the task. The present study suggests that cognitive impairments in aged monkeys can be compensated for by employing behavioral strategies.     

Developmental changes in food transfers in cotton-top tamarins (Saguinus oedipus)

We investigated the development of food transfer and independent feeding in cotton-top tamarin (Saguinus oedipus) families. We studied the relationship between infant-directed vocalizations and food transfers on the development of independent feeding in infants. We experimentally tested ten infants (eight twins and two singletons) three times a week for 17 weeks from before weaning through 20 weeks. Food transfers and vocalizations made during tests were recorded and analyzed to determine (1) the role of vocalizations (C- and D- chirps and D-chirp series) in food acquisition, (2) the relationship between food transfers and individual food acquisition, and (3) whether, owing to energetic costs of nursing and carrying twins, food is transferred to twins sooner than to singletons. Infants were more successful in acquiring food via begging when adults produced repeated vocalizations than when adults did not vocalize. Adults emitted more food-related vocalizations in rapid series when in the presence of infants, whereas during feeding in the absence of infants only single unit vocalizations were produced. Begging occurred frequently. Changes over infant age were not significant when all infants were included in analysis. However, when twin data were analyzed alone, begging success changed significantly over months, with successful begging peaking in month 3 (week 12). Begging success rate did not differ between twins and singletons, although twins fed independently sooner and at a higher rate than did singletons.     

The window and mechanisms of major age-related decline in the production of new neurons within the dentate gyrus of the hippocampus

While it is well known that production of new neurons from neural stem/progenitor cells (NSC) in the dentate gyrus (DG) diminishes greatly by middle age, the phases and mechanisms of major age-related decline in DG neurogenesis are largely unknown. To address these issues, we first assessed DG neurogenesis in multiple age groups of Fischer 344 rats via quantification of doublecortin-immunopositive (DCX+) neurons and then measured the production, neuronal differentiation and initial survival of new cells in the subgranular zone (SGZ) of 4-, 12- and 24-month-old rats using four injections (one every sixth hour) of 5'-bromodeoxyuridine (BrdU), and BrdU-DCX dual immunostaining. Furthermore, we quantified the numbers of proliferating cells in the SGZ of these rats using Ki67 immunostaining. Numbers of DCX+ neurons were stable at 4-7.5 months of age but decreased progressively at 7.5-9 months (41% decline), 9-10.5 months (39% decline), and 10.5-12 months (34% decline) of age. Analyses of BrdU(+) cells at 6 h after the last BrdU injection revealed a 71-78% decline in the production of new cells per day between 4-month-old rats and 12- or 24-month-old rats. Numbers of proliferating Ki67+ cells (putative NSCs) in the SGZ also exhibited similar (72-85%) decline during this period. However, the extent of both neuronal differentiation (75-81%) and initial 12-day survival (67-74%) of newly born cells was similar in all age groups. Additional analyses of dendritic growth of 12-day-old neurons revealed that newly born neurons in the aging DG exhibit diminished dendritic growth compared with their age-matched counterparts in the young DG. Thus, major decreases in DG neurogenesis occur at 7.5-12 months of age in Fischer 344 rats. Decreased production of new cells due to proliferation of far fewer NSCs in the SGZ mainly underlies this decline.     

Major Changes in a Rhythmic Ball-Bouncing Task Occur at Age 7 Years

The aim of the study was to investigate the development of a rhythmical skill of children aged from 5 to 12 years old. Five age groups (5–6, 7–8, 9–10, 11–12, and young adults) performed a virtual ball bouncing task (16 forty-second long test trials). Task performances, racket oscillation, ball-racket impacts as well as the ball-racket coupling were analysed. The results showed a change in both performance and behaviour at the age of 7 years old. Before this age, children exhibited restricted perceptual-motor coordination with a high frequency of racket oscillation and a poor level of performance. After the age of 7, cycle-to-cycle adaptive coordination based on visual information was progressively acquired leading to increasing performance levels with age. Overall these results revealed a rapid change in capability to perform the ball bouncing task across age with a late emergence of the required coordination and significant change in the coordination at the age of 7.     

Social play behavior in infant Sichuan snub-nosed monkeys (Rhinopithecus roxellana) in Qinling Mountains, China

We describe the development of social play behavior and assess factors influencing the development of play in infant Sichuan snub-nosed monkeys (Rhinopithecus roxellana). Infant snub-nosed monkeys began to exhibit social play at 3 months of age, when they spent an average 0.89% of time engaging in this behavior (range: 0.7-1.12%). At 6 months of age, there was a significant increase in the proportion of time spent in social play, averaging 9.78% of observation time (range: 4.92-17.08%). However, from 7 to 9 months of age during the winter, social play decreased gradually before rising again from 10 months of age in the spring. Play behavior in infant snub-nosed monkeys is influenced by environmental temperature. Males were observed to play more than females, although further data on this are required. Social rank did not influence the social play of wild Sichuan snub-nosed monkey infants.     

Characteristics of functional asymmetry in small premature infants at an age of 13–14 months

Delayed consequences of a sharp shortening of the prenatal period for the formation of handedness and the function of visuospatial attention were analyzed. The test group consisted of 16 small premature (SP) children at a corrected age of 13–14 months. The functional asymmetry was assessed by means of the A-not-B neuropsychological task, which is arranged in such a way that a child has to look for an attractive object in either a left or a right location. As compared to healthy children of the same age, the functional asymmetry of SP children was characterized by the absence of right-handedness. During the performance of the A-not-B trials, the SP children displayed a distinct left-side asymmetry: trials with an object hidden to the right of the child were significantly more frequently erroneous than those with a left-side position of the object. It is suggested that SP children have problems with disengagement of the attentional focus from an object located in the left half-field of vision under the conditions of shifting the attention to the right half-field. Probably, one of the consequences of a sharp decrease in the period of prenatal development is abnormal lateralization of some brain functions.     

Plasma progesterone, androstenedione and testosterone concentrations in freemartin heifers.

Plasma concentrations of testosterone, androstenedione and progesterone in freemartins, and normal cyclic and non-cyclic heifers were studied. The plasma testosterone concentrations were in general less than 10 pg/ml in all animals. The mean androstenedione concentration of 28 pg/ml in 10- to 12-month-old freemartins was significantly lower than the mean of 58 to 60 pg/ml for normal 10- to 12-month-old heifers. At 24 months of age the mean androstenedione concentration in the freemartins had risen significantly to 65 pg/ml.     

Age-related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild-type mice

We assessed baseline and KCl-stimulated glutamate release by using microdialysis in freely moving young adult (7 months) and middle-aged (17 months) transgenic mice carrying mutated human amyloid precursor protein and presenilin genes (APdE9 mice) and their wild-type littermates. In addition, we assessed the age-related development of amyloid pathology and spatial memory impaired in the water maze and changes in glutamate transporters. APdE9 mice showed gradual spatial memory impairment between 6 and 15 months of age. The stimulated glutamate release declined very robustly in 17-month-old APdE9 mice as compared to 7-month-old APdE9 mice. This age-dependent decrease in stimulated glutamate release was also evident in wild-type mice, although it was not as robust as in APdE9 mice. When compared to individual baselines, all aged wild-type mice showed 25% or greater increase in glutamate release upon KCl stimulation, but none of the aged APdE9 mice. There was an age-dependent decline in VGLUT1 levels, but not in the levels of VGLUT2, GLT-1 or synaptophysin. Astrocyte activation as measured by glial acidic fibrillary protein was increased in middle-aged APdE9 mice. Blunted pre-synaptic glutamate response may contribute to memory deficit in middle-aged APdE9 mice.     

Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice

The P2X7 receptor is an ATP-gated cation channel expressed by a number of cell types. We have shown previously that disruption of P2X7 receptor function results in downregulation of osteogenic markers and upregulation of adipogenic markers in calvarial cell cultures. In the present study, we assessed whether loss of P2X7 receptor function results in changes to adipocyte distribution and lipid accumulation in vivo. Male P2X7 loss-of-function (KO) mice exhibited significantly greater body weight and epididymal fat pad mass than wild-type (WT) mice at 9 months of age. Fat pad adipocytes did not differ in size, consistent with adipocyte hyperplasia rather than hypertrophy. Histological examination revealed ectopic lipid accumulation in the form of adipocytes and/or lipid droplets in several non-adipose tissues of older male KO mice (9–12 months of age). Ectopic lipid was observed in kidney, extraorbital lacrimal gland and pancreas, but not in liver, heart or skeletal muscle. Specifically, lacrimal gland and pancreas from 12-month-old male KO mice had greater numbers of adipocytes in perivascular, periductal and acinar regions. As well, lipid droplets accumulated in the renal tubular epithelium and lacrimal acinar cells. Blood plasma analyses revealed diminished total cholesterol levels in 9- and 12-month-old male KO mice compared with WT controls. Interestingly, no differences were observed in female mice. Moreover, there were no significant differences in food consumption between male KO and WT mice. Taken together, these data establish novel in vivo roles for the P2X7 receptor in regulating adipogenesis and lipid metabolism in an age- and sex-dependent manner.     

The role of the genotype in the variability of human evoked potentials at different stages of ontogeny]

The determinants of individual differences in visual EPs to stimuli of different type depending on the age of subjects were studied. EPs to flash, checkerboard pattern and some other stimuli with semantic aspect were recorded in three groups of MZ, DZ twins aged 8-9, 10-12, 18-25 years. The heritability of EPs parameters is not ontogenetically stable characteristic. It changes from one age group to another in different way for separate EPs components and parameters depending on their nature, type of stimulus, area of recording. Most of all genotypical influences are manifested in EPs parameters of 10-12 years old subjects, especially the middle latency components from vertex area and latent periods of EPs in comparison with their amplitudes.     

Aging is associated with increased clonogenic potential in rat liver in vivo

Cancer increases with age and often arises from the selective clonal growth of altered cells. Thus, any environment favoring clonal growth per se poses a higher risk for cancer development. Using a genetically tagged animal model, we investigated whether aging is associated with increased clonogenic potential. Groups of 4-, 12-, 18-, and 24-month-old Fischer 344 rats were infused (via the portal vein) with 2x10(6) hepatocytes isolated from a normal syngenic 2-month-old donor. Animals deficient in dipeptidyl-peptidase type IV (DPP-IV-) enzyme were used as recipients, allowing for the histochemical detection of injected DPP-IV+ cells. Groups of animals were sacrificed at various times thereafter. No growth of DPP-IV+ transplanted hepatocytes was present after either 2 or 6 months in the liver of rats transplanted at young age, as expected. In striking contrast, significant expansion of donor-derived cells was seen in animals transplanted at the age of 18 months: clusters comprising 7-10 DPP-IV+ hepatocytes/cross-section were present after 2 months and were markedly enlarged after 6 months (mean of 88+/-35 cells/cluster/cross-section). These results indicate that the microenvironment of the aged liver supports the clonal expansion of transplanted normal hepatocytes. Such clonogenic environments can foster the selective growth of pre-existing altered cells, thereby increasing the overall risk for cancer development associated with aging.